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THE  CLINICAL  PATHOLOGY 

OF 

SYPHILIS  AND  PARASYPHILIS 


PLATE  I. 


Fig.  I. — Serum  from  Scraping  of  a  Chancre,     (P.  Gastou.) 

Numerous  Spirochcsta  pallida  are  seen.  Above  one  Spirochcsta 
refringens  with  very  open  spiral  is  seen.  Three  epitheUal 
cells  and  several  red  blood-cells  (fine  circles)  are  present. 


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THE  CLINICAL  PATHOLOGY 

OF 

SYPHILIS  ^  PARASYPHILIS  ^ 

AND    ITS    VALUE    FOR 

DIAGNOSIS  AND  CONTROLLING 
TREATMENT 


BY 

T.UGH  WANSEY  BAYLY,  M.A.,  M.R.C.S.,  L.R.C.P. 

PATHOLOGIS'f  TO   THE   LONDON   LOCK    HOSPITALS 
CLINICAL    PATHOLOGIST  TO   THE   NATIONAL   HOSPITAL    FOR   THE    PARALYZED 

AND   EPILEPTIC 
ASSISTANT   IN   THE    BACTERIOLOGICAL   DEPARTMENT   OF   ST.    GEORGE's   HOSPITAL 


NEW  YORK 

WILLIAM     WOOD     «&     COMPANY 

MDCCCCXII 


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TO 


CHARLES  SLATER,  M.A.,  M.B.,  F.C.S., 

Director  of  the  Clinical  Laboratories  of,  and  Bacteriologist  {since  1889) 

to,  St.  George's  Hospital  ; 

Reader  in  Bacteriology  to  the  University  of  London , 

WITH  HIS  PUPIL'S  GRATITUDE  AND  HOMAGE. 


\ 


AUTHOR'S  PREFACE 

This  little  book  is  intended  for  the  use  of  the  general 
practitioner  and  medical  student,  and  not  in  any  way 
as  a  book  of  reference  for  the  pathologist.  I  have 
frequently  been  asked  by  students  and  practitioners  if 
I  could  tell  them  of  a  small  book  containing  the 
essentials  of  the  clinical  pathology  of  syphilis,  and  I 
hope  this  little  book  will  meet  that  demand.  I  have 
endeavoured  to  collect  and  review  the  essential  points 
in  the  clinical  pathology  of  syphilis  and  parasyphilis 
and  to  present  them  in  such  a  manner  as  to  emphasize 
their  practical  value  for  diagnosis  and  treatment. 
Theory  has  been  omitted  as  much  as  possible,  as  have 
also  detailed  accounts  of  research  and  experimental 
work.  The  literature  on  this  subject  is  immense,  and 
I  have  made  no  bibliography  in  this  volume.  The 
majority  of  the  references,  however,  will  be  found  in 
the  books  referred  to  below,  or  in  articles  by  others 
and  myself  that  have  appeared  within  the  last  three 
years  in  the  Lancet,  the  Practitiorier,  the  Bvitish  Medical 

vii 


viii  AUTHOR'S  PREFACE 

Journal,  and  the  Quarterly  Journal  of  Medicine.  Readers 
wishing  for  greater  details  will  find  them  in  the 
works  mentioned  on  p.  185,  from  which  I  have  freely 
borrowed.  HUGH  WANSEY  BAYLY. 

Bacteriological  Department, 

St.  George's  Hospital,  S.W. 
July,  1912. 


INTRODUCTION 

Syphilis  at  the  present  time  furnishes  an  excellent 
example  of  the  value  of  the  scientific  use  of  the  imagina- 
tion and  of  modern  methods  of  research  in  the  elucida- 
tion of  the  etiology  of  a  disease,  and  in  the  discovery 
of  means  for  diagnosis  and  treatment. 

Before  1903  an  enormous  amount  of  valuable 
material  had  been  collected  by  the  clinicians,  the 
various  stages  and  manifestations  of  the  disease  were 
well  known,  the  obscure  relations  existing  between 
syphilis  and  certain  nervous  diseases  had  been  un- 
ravelled with  the  greatest  ingenuity,  and  certain  lines 
of  treatment  had  been  discovered  and  adopted  with 
success.  This  material  did  not,  however,  acquire  its 
full  value  until  Roux  and  Metchnikoff  showed  that 
syphilis  could  be  transferred  to  the  lower  animals,  and 
could  thus  be  subjected  to  experimental  conditions, 
and  until  Schaudinn  in  1905  had  discovered  the  cause 
in  the  Spirochista  pallida,  and  thus  provided  an  in- 
fallible means  of  determining  the  true  nature  of  a 
suspicious  lesion. 

From  a  series  of  bacteriological  observations  made 

ix 


X  INTRODUCTION 

in  connection  with  the  study  of  immunity,  and  remote 
alike  from  syphilis  and  considerations  of  practical 
medicine,  sprang  that  most  valuable  of  diagnostic 
methods,  the  Wassermann  reaction,  whose  reliability 
now  rests  on  a  solid  basis  of  experience. 

This  disease  also  furnishes  an  example  of  the 
deliberate  experimental  search  for  a  drug  which, 
while  harmless  to  the  patient,  should  be  capable  of 
destroying  the  causal  organism,  a  search  which,  as  is 
well  known,  ended  in  the  discovery  of  Salvarsan. 

As  is  to  be  expected,  these  new  discoveries,  which 
give  rise  to  hopes  that  we  might  control  if  not  eliminate 
a  disease  so  widely  spread,  so  often  recurring  during 
many  years  of  a  patient's  life,  and  of  such  social  im- 
portance, are  naturally  of  the  greatest  interest  and 
importance,  and  have  been  the  subjects  of  innumer- 
able investigations,  so  that  the  literature  of  the  subject 
is  enormous.  Some  guide,  therefore,  is  wanted  by  the 
practitioner  w^hich  shall  sift  the  observations  which 
are  of  practical  importance,  and  which  shall  show  him 
how  to  apply  this  recent  knowledge  to  the  study  of 
his  own  cases.  It  is  the  intention  of  this  book  to 
provide  such  a  guide,  and  to  consider  our  clinical 
knowledge  of  the  disease  in  relation  to  these  new^ 
diagnostic  and  therapeutic  measures. 

CHARLES  SLATER. 


CONTENTS 


CHAPTER  I  PAGE 

Parasitology  ......        i 

History  of  parasitology — Character  oi  Spirochata pallida — 
Granule  shedding — Agglutination — Spirolysins — Vis- 
cosity— Examination  of  fresh  and  stained  preparations 
— Differential  diagnosis  of  various  spirochaetae — Im- 
portance of  early  diagnosis — Reliability  of  micro- 
scopical diagnosis 

CHAPTER  II 

Parasitology — Continued,      -  -  -  -  -      20 

Culture  of  Spitochata  pallida — Habitat — Inoculation — In- 
cubation period — Reinfection— Immunity 

CHAPTER  III 

Syphilitic  Anaemias  -  -  -  -  -      37 

Red  cells,  leucocytes,  haemoglobin — Types  of  anaemia  in 
adults  —  Types  of  anaemia  in  infants  —  Ansemia  of 
different  stages  of  syphilis 

CHAPTER  IV 
Theories  for  and  Nature  of  Wassermann  Reaction      46 

Pfeiffer's  phenomenon — Antigen  -  antibody  reactions  — 
Complement  fixation — Bordet-Gengou  phenomenon 
— Wassermann  reaction 

CHAPTER  V 

Preparation    and    Titration    of    Reagents    required 

FOR  Wassermann  Reaction     -  .  -  -       59 

Syphilitic  Pseudo-antigen  —  Test-serum  —  Complement 
Hsemolytic  system  :  {a)  sheep's  corpuscles,  (6)  haemo- 
lytic  serum 

xi 


xii  CONTENTS 

CHAPTER  VI  PAGE 

Wassermann  Reaction,  Original  Technique    -  -      70 

Quantitative  measurement  by  variation  in  amount  of  com- 
plement— The  Wassermann-Neisser  original  technique 
—  Quantitative  measurement  of  complement  -  fixing 
body  —  (a)  By  variation  in  amount  of  complement, 
{b)  by  variation  in  amount  of  test-serum,  [c)  with  a  S7nall 
amount  of  blood — Reasons  for  superiority  of  original 
technique 

CHAPTER  VII 

Wassermann  Reaction,  Simplified  Techniques  -      81 

Sources  of  error 

CHAPTER  VIII 

Wassermann  Reaction,  Specificity  of  Reaction         -       86 

Reaction  in  conditions  other  than  syphilitic — Wasser- 
mann reaction  at  the  various  stages  of  infection 

CHAPTER  IX 

Cerebro-Spinal  Fluid         -  -  -  -  -      96 

Lumbar  puncture  —  Cytological  examination  —  Wasser- 
mann reaction — Chemical  examination 


CHAPTER  X 

Urine  -  -  -  -  -  -  -  -     no 

Acute  syphilitic  nephritis — Subacute  syphilitic  nephritis 
— Chronic  syphilitic  nephritis — Lardaceous  disease  of 
the  kidney 

CHAPTER  XI 
Clinical  Value  of  Wassermann  Reaction        -  -    113 

(a)  In  latent  syphilis — (b)  For  differential  diagnosis — (c) 
For  controlling  treatment — (d)  As  regards  marriage  and 
offspring 


CONTENTS  xiii 

CHAPTER  XII  PACE 

Serum  and  Cerebro-Spinal  Fluid  in  Nervous  Diseases     123 

General  paralysis — Tabes  dorsalis — Cerebral  syphilis — 
Mental  deficiency — Differential  diagnosis 


CHAPTER  XIII 
Treatment     ...---.     135 

(i)  Salvarsan  :  Method  of  administration — Dosage — 
Therapeutic  results  in  different  stages  — After-effects — 
Relapses  —  Contra  -  indications  —  Conclusions  —  (2) 
Mercury 

CHAPTER  XIV 

Effect  of  Treatment  on  the  Wassermann  Reaction 

BY  Mercury  and  Salvarsan    -  .  .  -     159 

Mercury  :  Pills,  suppositories,  inunction,  intramuscular 
injection — Salvarsan  :  Intramuscular  injection — Intra- 
venous injection 

CHAPTER  XV 

Anaphylaxis  and  Syphilis  ...  -     172 

Anaphylaxis  —  Arthus  phenomenon  —  Theobald  Smith 
phenomenon — Noguchi's  luetin  reaction 


CHAPTER  XVI 

Life  Insurance  and  the  Wassermann  Reaction  -     179 

Registrar-General's  report :  Deaths  from  syphilis  alone 
—Deaths  from  diseases  syphilitic  in  origin— Deaths 
from  diseases  partly  attributable  to  syphilis — Deaths 
in  which  syphilis  may  be  a  contributing  cause — In- 
creased mortality-rate  amongst  syphilitics 


Index  --------    186 


CHAPTER  I 

PARASITOLOGY 

History  of  Parasitology. — Since  the  occurrence 
of  the  historical  epidemic  of  syphilis  that  spread 
over  Europe  in  1495,  the  contagious  character  of  the 
disease  has  been  recognized,  and  this  was  verified  by 
means  of  experiments  by  Hunter  in  1778.  In  1819 
Swediaur  put  forward  the  suggestion  that  the  syphilitic 
virus  was  a  ferment  spreading  by  the  lymphatics  and 
so  infecting  the  lymphatic  glands,  and  that  the  action 
of  this  ferment  was  capable  of  producing  ulcerations. 
Donne,  in  1837,  made  the  first  bacteriological  re- 
searches of  syphilitic  ulcerations  and  demonstrated  the 
presence  of  spirilla,  which  he  considered  were  the  causal 
organisms.  Klebs,  in  1878,  described  small  bodies 
which  he  named  '  helicomonades,'  resembling  small 
grains  or  short  rods,  which  were  easy  to  cultivate,  and 
which  he  said  produced  syphilitic  lesions  in  animals. 
Lustgarten,  in  1884,  discovered  a  bacillus,  somewhat 
like  the  tubercle  bacillus,  in  chancres,  papules, 
enlarged  glands,  and  gummata.  This  bacillus  was 
more  easily  decolourized  than  the  tubercle  bacillus, 
and  was  about  3  to  4  /a  long  and  0*3  fx  broad.  It  was 
stained  by  means  of  a  solution  of  gentian  violet, 
heated  to  40°  C.  for  two  hours,  and  the  preparation 


2  SYPHILIS  AND  PARASYPHILIS 

then  decolourized  by  a  mixture  of  permanganate  of 
potash  and  sulphuric  acid,  and  dehydrated  by  alcohol, 
when  the  Lustgarten  bacillus  remained  stained. 
Lustgarten's  results  were  confirmed  by  Doutrelepont 
and  Giacomi,  who  used  i  per  cent,  solution  of  gentian 
violet  and  decolourized  for  a  few  seconds  in  a  dilution 
of  acetic  acid  and  then  in  60  per  cent,  alcohol.  In 
1896  Neisser  discovered  a  polymorphic  bacillus  in  the 
blood  of  syphilitics.  In  1897  P^^^  cultures  of  the 
bacillus  of  smegma  were  obtained  by  Laser  and 
Czaplewsky,  who  considered  that  this  might  be  the 
causal  organism  of  syphilis. 

The  above  are  only  a  few  of  the  organisms  claimed 
by  their  discoverers  to  have  been  the  cause  of 
syphilis,  but  there  was  never  sufficient  evidence  of 
their  specificity  to  satisfy  the  profession  at  large. 

In  1905  Schaudinn  discovered  a  thin  spiral 
organism  which  could  be  demonstrated  in  Hunterian 
chancres  in  practically  every  case.  He  gave  this 
organism  the  name  of  Treponema  pallidum,  on  account 
of  its  slight  refractive  and  staining  qualities,  which, 
combined  with  its  extreme  tenuity,  rendered  it  difficult 
of  demonstration  by  most  methods  of  staining.  This 
organism  was  so  constant  in  its  appearance  and  char- 
acteristics that  Schaudinn  was  able  to  write : 

*  It  is  easy,  after  a  certain  amount  of  diligence,  to 
differentiate  the  Treponema  pallidum  from  other  types  of 
spirochsetes  in  fresh  preparations.  The  fineness  and 
feeble  refractility  of  this  spirochaete,  the  constant, 
close,  deep,  and  regular  character  of  its  spirals  which 
are  numerous  (10  to  20),  render  it  impossible  to  confuse 
it  with  other  micro-organisms  of  the  same  type.  Its 
chief  characteristic,  however,  lies  in  the  fact  that  it 


PARASITOLOGY  3 

retains  its  spiral  arrangement  not  only  during  move- 
ment, but  also  in  the  state  of  rest,  while  the  spirals  of 
most  of  the  other  spirochsetes  disappear  when  they  are 
in  the  condition  of  repose.' 

This  description  of  Schaudinn's  still  holds  good, 
and  makes  it  one  of  the  easiest  organisms  to  diagnose 
in  fresh  preparations.  As  its  characteristic  movements 
are  one  of  its  diagnostic  features,  it  is  best  examined 
by  the  dark-ground  illumination  method  (ultra-micro- 
scope), which  is  the  only  satisfactory  means  of  examin- 
ing the  organism  alive. 

Characters  of  Spirochaeta  Pallida.  —  When 
examined  by  dark-ground  illumination,  its  charac- 
teristic appearance  is  that  of  an  extremely  fine, 
silvery  spiral  from  5  to  25  /x  in  length,  with  very 
regular  and  closely  set  spirals  (about  seven  to  the 
diameter  of  a  red  blood-disc),  the  distance  between  the 
spirals  being  i  /x.  The  number  of  the  spirals  range 
from  5  to  25,  and  the  extremities  of  the  organism  are 
pointed.  It  may  happen  that  the  light  is  only  reflected 
from  the  summit  of  the  spirals,  in  which  case  the 
organism  will  have  the  appearance  of  a  chain  of  equi- 
distant luminous  dots  not  unlike  a  chain  of  streptococci. 
By  careful  focussing,  however,  this  chain  of  dots 
will  be  seen  to  be  a  spiral  (see  Figs,  i  and  2).  The 
living  Spirochcdta  pallida  preserves  a  helicoidal  form, 
but  as  its  vitality  diminishes  the  spiral  tends  to  dis- 
appear. 

In  serum,  but  never  in  water,  giant  forms  up  to  45  ju 
are  sometimes  seen ;  these  are  probably  formed  by 
several  spirochsetae  becoming  attached  end  to  end. 
This  Dr.  Comandon  describes  as  *  linear  agglutination.' 


4  SYPHILIS  AND  PARASYPHILIS 

If  a  drop  of  water  is  added  they  are  seen  to  break  up 
into  several  organisms. 

The  movements  are  more  active  and  last  longer  in 
the  patient's  own  serum  than  in  distilled  water  or 
saline.  In  serum,  also,  the  movements  are  more 
rapid  and  the  spirals  closer  together  than  in  water. 
The  movements  vary  with  the  vitality,  and  are 
increased  by  warming  the  preparation. 

In  water  the  Spirochata  pallida  is  but  feebly  motile 
compared  with  most  of  the  other  spirochaetse  met  with. 
If  there  is  no  current  in  the  fluid  the  spirochaete  will 
remain  in  the  field  for  a  long  time.  Care  must  be  taken 
to  distinguish  the  movements  proper  to  the  organism 
from  those  imparted  to  it  by  a  current  of  the  fluid 
in  which  it  is  being  examined.  It  preserves  its  spirals 
during  rest,  while  all  other  analogous  spirochsetes, 
which  present  marked  undulations,  show  them  only 
when  they  are  moving  vigorously,  and  when  at  rest 
they  have  long,  flattened-out  undulations,  and,  indeed, 
are  very  nearly  straight.  This  peculiar  appearance  of 
the  Spirochata  pallida  is  due  to  the  fact  that  in  it  the 
spiral  arrangement  is  permanent,  whilst  in  other 
varieties  the  deep  spiral  is  only  produced  during  rapid 
movement,  and  is  straightened  out  at  rest.  There  is 
only  one  spirillum,  that  of  the  mouth  or  Spirochata 
denthmi  which  has  a  small  fixed  spiral  arrangement, 
but  this  variety  can  be  distinguished  by  other 
characteristics  from  the  organism  of  syphilis.  No 
undulating  membrane  has  yet  been  demonstrated 
in  SpirochcBta  pallida. 

The  movements  consist  of — 

I.  Bending,  which  is  the  most  marked. 


PARASITOLOGY  5 

2.  Snake-like  undulations. 

3.  Rotation  round  its  long  axis  like  a  screw. 

4.  Concertina-like  movements,  by  which  the  spirals 
are  drawn  out  or  approximated,  so  that  organism 
becomes  lengthened  or  shortened  respectively. 

5.  Occasionally  a  local  wave  of  contraction  may  be 
seen  which  flattens  out  the  spirals.  This  movement 
is  very  rarely  seen  with  any  other  spirochsete  than 
Spirochceta  pallida. 

Schaudinn  considered  that  on  section  the  Spirochceta 
pallida  was  probably  round,  and  that  the  organism  was 
cylindrical  and  not  flattened,  as  is  the  case  with  most 
of  the  other  spirochaetae. 

The  peripheral  protoplasm  is  continued  at  each  end 
of  the  organism  in  the  form  of  a  cilium  whose  length 
equals  about  four  to  six  undulations.  The  largest 
Spirochceta  pallidcB  are  distinguished  by  the  presence  of 
two  cilia  at  one  pole.  Schaudinn  considered  that 
these  double  cilia  indicated  the  commencement  of 
longitudinal  division,  and  wrote  in  December,  1905  : 

'  I  have  already  succeeded  in  three  cases  in 
observing  the  longitudinal  division  of  the  organism. 
To  follow  out  this  process  I  have  chosen  individuals 
which  already  possessed  two  fine  cilia  at  one  of  the 
poles,  and  1  have  seen  the  longitudinal  division 
progressing  rapidly  after  beginning  at  this  pole.  At 
the  moment  of  division  the  organism  abandoned  its 
marked  spiral  form,  and  appeared  to  be  very  irregularly 
contorted.' 

The  question  whether  the  Spirochceta  pallida  is  to 
be  classed  with  the  bacteria  or  protozoa  has  still  to  be 
settled,  and  its  cycle  of  development  has  still  to  be 
demonstrated.      Krzyztalowicz   and    Siedelecki   think 


6  SYPHILIS  AND  PARASYPHILIS 

that  they  have  recognized  female  elements  in  the  form 
of  large  spirilla,  and  male  elements  in  the  form  of 
small  spirilla,  and  state  that  they  have  seen  these  two 
elements  unite. 

A.  Neisser  hazards  the  opinion  that  there  may  exist 
an  unknown  stage  of  development,  or  rest  stage,  of 
the  spirochsete,  analogous  to  the  spores  and  granular 
forms  of  many  bacteria,  which  may  be  far  more  diffi- 
cult to  influence  by  any  medicament  than  the  spiro- 
chaete  itself. 

The  possibility  of  this  theory  being  correct  is 
heightened  by  the  observations  of  Dr.  Reinke,  of 
Wiesbaden,  who  in  1910  demonstrated  granules  in  the 
lung  of  a  congenital  syphilitic  infant  in  an  autopsy 
performed  after  treatment  with  salvarsan.  He  con- 
sidered that  the  granules  were  derived  from  spiro- 
chaetes,  and  Dr.  A.  Balfour  is  of  the  opinion  that 
granule-shedding  in  Spirochata  pallida  occurs  before 
any  treatment  of  the  case  is  begun.  It  is,  therefore, 
in  all  probability,  a  feature  in  the  life-history  of  the 
spirochaete.  This  same  phenomenon  of  granule-shed- 
ding is  true  of  other  spirochaetes  associated  with  that 
of  syphilis,  and  is  especially  well  seen  in  the  case  of 
the  Spivochata  refringens.  Balfour  thinks  that  the 
granules  are  of  the  nature  of  resistant  spores,  that 
they  play  an  important  part  in  relapse,  and  that  they 
are  influential  factors  in  the  occurrence  of  the  later 
manifestations  of  syphilitic  infection. 

AGGLUTINATION 

The  Spivochceta  pallidce  may  be  preserved  in  normal 
saline  solution  for  several  hours  without  showing  any 


PARASITOLOGY  7 

traces  of  agglutination,  but  if  to  the  saline  solution  the 
filtered  product  of  a  chancre  or  syphilitic  papule  is 
added,  agglutination  is  at  once  produced. 

There  is  only  a  feeble  agglutination  if  the  serum  of 
the  same  individual  is  used,  showing  that  the  agglutinins 
are  present  in  smaller  quantity  in  the  serum  than  in 
the  fluids  immediately  surrounding  aggregations  of 
spirochaetae. 

Agglutination  has  been  observed  in  the  blood  in 
very  intense  general  infection. 

Agglutination  phenomena  are  most  clearly  observed 
in  the  serum  during  the  period  of  the  rash. 

Agglutination  has  never  been  seen  at  a  higher  dilu- 
tion than  I  in  i,ooo,  and  usually  only  occurs  in  a 
dilution  of  i  in  lo. 

SPIROLYSIS 

Spirolysins — that  is  to  say,  substances  having  the 
property  of  dissolving  spirochaetae — have  also  been 
observed  in  the  serum,  and  clumps  of  agglutinated 
spirochaetes  after  some  time  become  granular,  of 
irregular  form,  and  finally  disappear,  whereas  control 
specimens,  treated  with  normal  serum  or  salt  solution 
instead  of  specific  serum,  preserve  their  shape  for 
several  days  or  even  weeks. 

VISCOSITY 

In  fresh  serum  the  spirochaete  pushes  past  any  solid 
object  that  it  touches,  but  as  it  becomes  less  mobile  it 
develops  a  tendency  to  stick  to  any  such  object. 


8  SYPHILIS  AND  PARASYPHILIS 

MICROSCOPICAL  EXAMINATIONS 

I.  Dark-Ground  Illumination. —By  means  of  a 
disc  of  black  enamel  painted  on  the  under  surface  of 
the  condenser  (see  Fig.  3),  all  rays  of  light  from  the 


Fig.  3. — Under  View  of  Ultra-Microscope,  showing  Lens 
IN  Centre  (White),  with  Black  Enamel  Disc  fainted 
ON  IT.  The  two  Centring  Screws  and  the  Spring  are 
also  shown. 

microscope  mirror,  with  the  exception  of  those  at  the 
periphery  of  the  condenser,  are  cut  off.  Those  passing 
through  the  clear  periphery  are  deflected  by  suitably 


Fig.  4. — Upper  Surface,  showing  Concentric  Circles 
scratched  on  it,  by  means  of  which  it  can  be 
rapidly  and  accurately  centred. 

cut  lenses  so  that  they  converge  obliquely  on  the 
object  examined,  which  appears  as  a  bright  refractive 
body  on  a  dark  background.     In  this  way  very  trans- 


PARASITOLOGY  g 

parent  objects,  which  are  invisible  by  direct  illumina- 
tion, are  easily  seen,  and  their  shape  and  movements 
,  studied. 

On  the  upper  surface  of  the  condenser  are  lightly 
scratched  several  concentric  circles,  by  means  of  which, 
using  a  i-inch  or  |-inch  objective  and  a  No.  i  or  2 


Slide  and  cover-glass,     t^ 


Stop. 


Ultra-microscope. 


Fig.  5. — Section  of  Objective  showing  'Stop,'  and  of 
Reflecting  Conversion  Condenser. 

The  black  line  below  the  condenser  represents  section  of 
the  black  enamel  disc. 


eyepiece,  the  apparatus  can  be  readily  centred  (see 

Fig.  4)- 

An  ordinary  ^^  oil-immersion  objective  admits  too 
much  light,  and  a  special  mount  for  the  lenses,  con- 
taining a  stop,  is  required.  A  sectional  diagram  of 
the  condenser  and  objective  with  stop  is  shown  in 
Fig.  5.     It  will  be  seen  that  no  rays  from  the  source 


PLATE  II. 


Fig.  2. — Scraping  from  Centre  of  a  Syphilitic  Chancre. 
Dark-Ground  Illumination.     (J.   Comandon.) 

In  centre  is  seen  a  mass  of  epithelial  debris  containing  numerous 
Spirochatid  pallidcs.  Below  free  Spirochceto  pallida  are  seen. 
Above  and  to  right  some  bacilli  are  seen. 


To] ace  p.  n. 


PARASITOLOGY  ii 

now  gently  scraped  until  blood  just  begins  to  exude. 
The  surface  is  now  again  dried  with  some  sterile 
gauze,  and  a  little  blood  or  serum  expressed.  A 
small  drop  of  this  is  removed  with  a  platinum  needle, 
and  mixed  with  a  drop  of  distilled  water  on  a  thin 
glass  slide.  If  this  slide  is  too  thick,  the  rays  of  light 
may  come  to  a  focus  below  the  surface,  and  an  un- 
satisfactory illumination  be  obtained.  A  large  cover- 
glass  is  now  pressed  down  firmly  so  that  only  a  thin 
layer  of  the  fluid  remains  between  the  slide  and  cover- 
glass.  This  can  be  conveniently  done  by  spreading 
a  piece  of  lint  over  the  knee  and  holding  the  slide  by 
each  end,  with  the  cover-glass  downwards,  and  press- 
ing it  against  the  knee  till  the  superfluous  fluid  is 
squeezed  out  and  absorbed  by  the  lint.  After  use  the 
lint  can  be  destroyed.  A  drop  of  immersion  oil  is  now 
placed  below  the  slide  and  also  on  the  upper  surface  of 
the  cover-glass.  The  slide  is  now  placed  in  position 
on  the  microscope  stage  so  that  the  drop  of  oil  on  the 
under  surface  touches  the  upper  surface  of  the  con- 
denser. The  j~  objective  is  now  lowered  into  the 
drop  of  oil  on  the  upper  surface  of  the  cover-glass  in 
the  usual  way.  The  condenser  must  now  be  racked 
up  or  down,  and  the  mirror  adjusted  until  bright 
illumination  with  a  dark  background  is  obtained. 

Distilled  water  is  the  best  medium  in  which  to 
examine  the  spirochsete,  as  by  osmosis  the  organism 
becomes  swollen  and  so  is  more  easily  seen  than  if 
examined  in  normal  saline  or  serum.  The  distilled 
water,  also,  by  producing  haemolysis  of  the  red  cells, 
gives  a  clearer  view  of  any  organism  that  may  be 
present.     After  about  half  an  hour,  the  spirochaete 


12  SYPHILIS  AND  PARASYPHILIS 

becomes  more  rigid  and  the  movements  sluggish,  and 
in  two  to  three  hours'  time  all  movement  ceases  in  the 
majority  of  cases. 

Phillips  and  Glynn  recommend  a  slightly  modified 
technique  for  the  collection  of  material  for  examination 
by  dark-ground  illumination.  The  primary  sore  is  first 
cleaned  with  absorbent  wool,  rubbed  with  the  wool, 
and  then  swabbed  two  or  three  times  with  wool  soaked 
in  methylated  spirit ;  in  a  minute  or  two  the  spirit  is 
wiped  off,  and  soon  clear  serum  begins  to  exude,  which 
is  collected  in  a  capillary  tube.  The  following  advan- 
tages are  claimed : 

(i)  There  is  very  little  or  no  blood. 

(2)  The  serum  washes  the  spirochsetes  from  the 
deeper  parts  where  they  are  more  constantly  present ; 
other  spirochsetes  and  bacteria  are  usually  absent. 

(3)  Plenty  of  material  is  obtained,  more  than  by 
any  other  way. 

2.  Bum's  Indian-Ink  Method. — The  ink  (Gun- 
ther- Wagner's)  must  be  well  centrifuged,  and  after 
the  coarser  particles  have  been  deposited  the  super- 
natent  fluid  containing  the  finer  particles  should  be 
pipetted  off  and  kept  in  a  stoppered  bottle. 

The  material  from  the  chancre  is  obtained  in  the 
same  way  as  that  for  the  dark-ground  illumination,  and 
a  drop  of  the  Indian-ink  suspension  is  used  instead  of 
distilled  water.  The  mixture  is  spread  in  a  thin  film 
and  allowed  to  dry  without  heat.  No  fixation  is 
required,  neither  is  a  cover-glass  necessary  unless  a 
permanent  specimen  is  desired. 

When  employing  Burri's  method,  Phillips  and  Glynn 
use  I  drop  of  serum  to  twice  the  volume  of  Indian  ink. 


PARASITOLOGY  13 

3.  Staining  of  Films. — Giemsa  Stain,  which  con- 
sists of  azur  II  eosin,  3  grammes;  azur  II,  8  grammes; 
chemically  pure  glycerine,  250  grammes  ;  and  methyl 
alcohol,  250  grammes.  The  following  are  Giemsa's 
directions : 

(i)  Fix  films  in  absolute  alcohol  from  fifteen  to 
twenty  minutes  ;  dry  with  filter-paper. 

(2)  Dilute  the  stain  with  distilled  water,  i  drop  of 
stain  to  i  c.c.  of  water,  the  mixture  being  well 
shaken. 

(3)  Stain  for  fifteen  minutes. 

(4)  Wash  in  a  brisk  stream  of  distilled  water. 

(5)  Drain  with  filter-paper,  dry,  and  mount  in  Canada 
balsam. 

The  SpirochtBta  pallida  should  appear  stained  rose- 
pink.  This  staining  reaction,  however,  is  not  invari- 
able, and  MetchnikofF  and  Roux  give  instances  where 
Spiyochata  pallidce,  obtained  from  the  experimental 
chancre  of  an  ape,  were  distinctly  blue  with  Giemsa's 
stain. 

Phillips  and  Glynn,  when  staining  by  Giemsa's 
method,  spread  a  drop  of  the  serum,  obtained  as  for 
dark-ground  illumination,  as  thin  as  possible  on  a  slide, 
and,  after  drying  and  fixing  in  absolute  alcohol,  it  was 
stained  face  downwards  with  Giemsa's  stain  diluted, 
I  in  8,  for  twelve  hours.  They  considered  this  long 
method  of  staining  the  most  reliable. 

Marino's  Stain. — The  films  are  first  dried  without 
being  fixed  in  any  way,  then  they  are  treated  with  a 
mixture  of  Marino's  blue  (o-i  gramme)  and  of  methyl 
alcohol  (20  c.c.) ;  after  three  minutes  some  drops  of  a 
watery  solution  of  eosin  (o'oo5  per  cent.)  are  added. 


14  SYPHILIS  AND  PARASYPHILIS 

Two  minutes  after  this  the  films  are  thoroughly  washed 
and  are  then  ready  to  be  examined. 

Loeffler's  Method  should  be  employed  to  show  the 
terminal  cilia.  A  freshly  made  mixture  is  used,  con- 
sisting of  10  c.c.  of  a  20  per  cent,  solution  of  tannin, 
5  c.c.  of  a  cold  saturated  solution  of  sulphate  of  iron, 
and  I  c.c.  of  saturated  alcoholic  solution  of  fuchsin. 
This  mixture  is  put  on  the  films  and  heated  three 
minutes  until  steam  comes  off.  It  is  then  washed  in 
distilled  water  and  stained  with  Ziehl's  solution  of 
carbol-fuchsin,  gently  heated  at  the  same  time.  By 
this  method  the  spirochaete  is  stained  a  dark  red,  while 
its  cilia  are  shown  in  a  light  rose  colour. 

Care  must  be  taken  in  all  these  methods  to  dilute 
the  syphilitic  products  with  some  drops  of  distilled 
water. 

Leishman's  Method.  —  A  film  dried  in  the  air 
and  not  fixed  is  treated  with  a  mixture  of  distilled 
water  and  Leishman's  stain  in  the  proportion  of 
2  parts  of  water  to  i  of  stain.  Optimum  staining 
takes  place  in  twenty-five  minutes,  when  the  stain 
must  be  washed  off  very  gently  with  distilled  water, 
and,  when  blotting  in  order  to  dry,  care  must  be  taken 
that  only  slight  pressure  is  used,  and  that  the  film  is 
not  rubbed. 

4.  Levaditi's  Silver  Method  for  Staining  Sec- 
tions.— (i)  Fix  small  pieces  of  tissue  in  10  per  cent, 
formalin  for  forty-eight  hours. 

(2)  Wash  for  an  hour  in  water. 

(3)  Keep  in  96  per  cent,  alcohol  for  twenty-four 
hours. 


PARASITOLOGY  15 

(4)  Place  in  a  1-5  solution  of  nitrate  of  silver  in  a 
dark  bottle. 

(5)  Incubate  at  37°  C.  for  three  days. 

(6)  Wash  in  water  for  twenty  minutes. 

(7)  Place  in  a  mixture  consisting  of  pyrogallic 
acid  4  parts,  formalin  5  parts,  distilled  water  up  to 
100  parts.  Keep  the  material  in  this  mixture 
in  a  dark  bottle  for  forty  hours  at  room  tempera- 
ture. 

(8)  Wash  in  water  for  a  few  minutes,  take  through 
an  increasing  strength  of  alcohol,  and  embed  in 
paraffin  in  the  usual  way. 

The  sections  ought  to  be  as  thin  as  possible.  In 
satisfactory  preparations  the  spirochaetae  appear  almost 
black  against  the  pale  yellow  background  of  the 
tissues. 

Differential  Diagnosis  of  Various  Spirochsetes 
likely  to  be  Confused  with  the  Spirochaeta 
Pallida. 

The  Spirochaeta  Refringens,  found  in  ulcerative 
lesions,  is  much  larger,  longer,  and  thicker  than  the 
Spifochceta  pallida^  the  curves  are  much  more  open  and 
shallow,  and  the  organism  moves  with  far  greater 
rapidity  (see  Fig.  7). 

The  Spirochaeta  Buccalis,  found  in  the  mouth,  is 
also  much  coarser,  and  is  quite  unlike  Spiyochceta  pallida 
(see  Fig.  8). 

The  Spirochaeta  Dentium,  found  in  carious  teeth, 
is  very  like  the  Spiyochceta  pallida,  but  it  is  shorter, 
being  only  5  to  10  /x,  and  the  depth  of  the  spirals  is 


i6 


SYPHILIS  AND  PARASYPHILIS 


considerably  less  than  in  the  SpirochcBta  pallida.     Like 
the  Spirochata  pallida^  it  retains  its  spirals  during  rest 
(see  Fig.  9). 
The  Spirochaeta  Pertenuis  of  Yaws,  described 


Fig.  7. — Spiroch.^ta 
Refringens. 


Fig.  8. — Spiroch^ta 
buccalis. 


Fig.  9, — Spiroch^ta 

DENTIUM. 


Fig.  10. — SpiROCHiETA 
Pseudo-Pallida. 


by  Castellani,  is  the  organism  most  like  that  of  syphilis, 
and  it  is  extremely  difficult,  if  not  impossible,  to 
distinguish  them  morphologically. 

The  Spirochaeta  Pseudo-Pallida  of  ulcerated 
cancerS;  described  by  Loewenthal,  does  not  appear  to 


PARASITOLOGY 


17 


justify  its  name,  as  it  is  not  very  like  the  true  pallida, 
and  is  not  likely  to  be  mistaken  for  it  except,  perhaps, 
in  badly  stained  films  (Fig.  lo). 

The  Spirochaeta  Balanitis  of  Hoffmann  is  a 
band-shaped  spirochaete  with  6  to  lo  twists,  is  0*5  to 
0*75  /x  broad,  with  an  undulating  membrane,  and  moves 
rapidly  backwards  and  forwards,  crossing  the  whole 
field  at  one  dash.  It  moves  by  snake-like  undulations 
or  by  screw-like  rotation  on  its  long  axis  (Fig.  11). 


Fig.  II. 


Fig.  12. 


Fig.  13. 


Other  spirochaetes  occasionally  seen  are  pictured  in 
Figs,  12  and  13. 

Diagnosis  by  Gland  Puncture.— Phillips  and 
Glynn  have  recorded  that  they  obtained  the  Spivochata 
pallida  in  37  per  cent,  of  cases  of  puncture  of  en- 
larged lymphatic  glands  corresponding  to  the  primary 
lesion. 

Preis  states  that  he  was  successful  in  nearly  100 
per  cent,  of  cases  in  the  secondary  latent  stage,  and 
that  he  never  failed  to  find  the  organism  during  the 
period  between  the  typical  hardening  of  the  glands 
and  the  first  appearance  of  a  rash. 


18  syPHILlS  AND  PARASYPHILIS 

Phillips  and  Glynn,  however,  state  that  they  never 
failed  to  find  the  spirochsete  in  the  primary  sore  in  any 
of  the  cases  when  they  found  the  organism  by  gland 
puncture. 

The  fact  that  gland  puncture  has  been  successfully 
performed  can  be  demonstrated  by  the  presence  of 
lymphocytes  in  the  material  obtained. 

Importance  of  Early  Diagnosis. 

In  the  absence  of  treatment,  a  sore,  the  nature  of 
which  is  clinically  doubtful,  can  in  a  few  moments  be 
demonstrated  to  be  clearly  syphilitic,  and  so  much 
valuable  time  may  be  saved,  and  the  annoyance  and 
discomfort  of  secondary  manifestations  prevented. 

Neisser  has  observed  that  the  earlier  in  the  course 
of  the  disease  that  treatment  is  commenced,  the  more 
probability  there  is  that  a  negative  serum  reaction 
will  be  obtained  after  a  course  of  treatment.  Thus, 
cases  showing  no  symptoms  of  syphilis  (early  latent) 
that  had  received  treatment  as  soon  as  possible  after 
the  primary  lesion  had  appeared,  give  a  negative  serum 
reaction  in  75  per  cent,  of  cases,  whereas  in  similar 
cases  in  which  the  treatment  had  not  been  commenced 
until  six  months  after  the  primary  lesion  occurred, 
only  33  per  cent,  of  cases  were  negative. 

By  early  treatment  the  period  of  infectivity  is 
shortened,  which  is  obviously  a  matter  of  the  greatest 
possible  importance  from  both  the  public  health  and 
social  points  of  view.  An  early  diagnosis  is  therefore 
of  paramount  importance,  both  to  the  patient  and  to 
those  with  whom  the  patient  is  brought  in  contact. 


PARASITOLOGY  19 

Reliability  of  Microscopical  Diagnosis. 

Either  general  or  local  treatment  has  a  marked 
effect  on  the  number  of  Spiwchcstce  pallidas  found,  and 
the  organisms  tend  to  disappear  from  the  site  of  the 
primary  inoculation  after  a  few  weeks,  even  without 
treatment.  If  a  local  antiseptic  has  been  applied,  the 
patient  should  be  instructed  to  wash  it  away  with  plain 
warm  water,  and  return  in  a  few  days'  time  for  another 
examination. 

As  with  most  pathological  findings,  however,  a 
positive  result  is  much  more  conclusive  than  a  negative 
one,  and  syphilis  cannot  be  put  out  of  court  till  three  or 
four  examinations  on  different  days  have  been  made, 
and  the  possibility  of  all  antisyphilitic  treatment, 
either  general  or  local,  excluded. 

Out  of  a  very  large  number  of  recent  untreated 
chancres,  very  few  have  failed  to  show  the  SpivochcBta 
pallida  when  examined  by  this  method.  The  demonstra- 
tion of  this  organism  in  primary  syphilis  is  therefore, 
from  a  diagnostic  point  of  view,  of  equal  importance 
to,  or  even,  perhaps,  of  greater  importance  than,  that 
of  Koch's  bacillus  in  pulmonary  tuberculosis  or  the 
Klebs-Loeffler  bacillus  in  diphtheria. 

The  use  of  this  method  of  diagnosis  has  shown  that 
sores  diagnosed  from  their  clinical  appearance  to  be 
non-syphilitic  were  really  syphilitic,  and  vice  versa — 
that  sores  considered  syphilitic  were  not  syphilitic.  No 
patient,  therefore,  should  be  condemned  as  a  syphilitic 
and  placed  on  antisyphilitic  treatment  on  the  clinical 
appearance  of  the  sore  alone,  but  only  after  demonstra- 
tion of  the  Spivochceta  pallida. 


CHAPTER  II 
PARASITOLOGY— Cow^ww^rf 

CULTURE  OF  SPIROCH^TA 

NoGucHi  claims  to  have  cultivated  the  Spiyochceta 
pallida  in  serum  water  (sheep's,  horse's  or  rabbit's)  to 
which  a  piece  of  sterile  rabbit  tissue  has  been  added. 
He  considered  the  rabbit  tissues  best  adapted  to  this 
purpose  are  the  kidney  and  testicle.  He  uses  test- 
tubes  20  cm.  high  and  ij  cm.  wide,  and  fills  them 
with  1 6  c.c.  of  serum  water,  i  part  serum  and 
3  parts  distilled  water.  After  completion  of  the  usual 
precautionary  sterilization  at  ioo°  C.  for  three  days, 
fifteen  minutes  each  day,  a  small  piece  of  freshly 
removed  sterile  tissue  is  placed  in  each  tube.  The 
tubes  are  incubated  at  37°  C.  for  two  days,  and  then 
examined  for  their  sterility.  To  each  tube  a  layer  of 
sterile  paraffin  oil  is  now  added  in  order  to  shield  the 
medium  from  contact  with  the  air  and  to  prevent 
evaporation.  Strict  anaerobic  conditions  are  very 
important  in  obtaining  the  first  generation  of  Spiro- 
chceta  pallida,  and  Noguchi  employs  a  combination 
of  hydrogen  gas,  vacuum,  and  pyrogallic  acid  in  an 
anaerobic  apparatus. 

To  obtain  the  first  generation  of  Spivochceta  pallida 
in  virulent  focm,  it  is  essential  that  there  should  be — 

20 


PARASITOLOGY  21 

1.  Suitable  fresh  sterile  tissue  in  serum  water. 

2.  Strict  anaerobic  conditions. 

3.  A  slightly  alkaline  reaction  furnished  by  the 
serum  and  tissue. 

4.  Temperature,  35°  to  37°  C. 

A  large  number  of  unsuccessful  attempts  will  be 
made  for  one  successful.  Noguchi  states  that  in  the 
serum  -  water  tissue  the  spirochaetse  commence  to 
multiply  after  forty-eight  hours,  and  continue  to  grow 
slowly  for  four  or  five  weeks.  He  states  that  in  the 
young  cultures  many  short  and  rather  heavy  specimens 
are  seen,  some  with  only  few  curves,  while  in  a  culture 
ten  or  twelve  days  old  the  spirochsetae  are  of  the  usual 
length  and  have  typical  curves.  As  they  grow  older 
the  spirochaetae  may  become  very  long  and  often  form 
a  tangled  mass.  Noguchi  also  states  that  of  two 
strains  of  pure  cultures  experimented  with,  both 
produced  typical  lesions  in  the  testicle  of  the  rabbit. 

HABITAT 

In  experimental  infection  the  spirochaetes  are  found , 
at  the  point  of  inoculation.  They  stay  in  its  immediate 
neighbourhood  for  a  certain  time  while  they  adapt 
themselves  to  their  new  environment  before  they 
commence  to  multiply.  .  They  irritate  the  tissues  by 
their  toxins,  and  provoke  a  characteristic  reactionary 
infiltration  and  development  of  the  connective  tissues. 
The  body-cells  oppose  to  the  spirochaetes  their  specific 
antitoxins,  to  which  the  spirochaetes  gradually  become 
accustomed.  They  then  develop  along  the  lymphatic 
vessels  and  invade  the  lymphatic  glands,  which  repre- 


22  SYPHILIS  AND  PARASYPHILIS 

sent  the  first  line  of  defence.     They  then  develop  in 
the  glands  and  provoke  a  reactionary  adenitis. 

The  spirochsetes  are  irregularly  distributed  in  the 
hard  chancre  and  in  the  lymphatic  glands.  In  the 
chancre  they  are  found  in  the  deeper  layers  around  the 
vessels  or  in  the  vessel  walls  In  the  glands  they  are 
unequally  disposed  in  groups,  which  explains  the  rarity 
of  their  presence  in  sections.  The  largest  masses  of 
spirochsetes  are  found  in  the  walls  of  the  vessels  and 
the  trabeculae  of  the  glands.  The  spirochsetes  pene- 
trate little  by  little  into  the  blood-stream. 

Agglomerations  of  spirochsetes  produce  embolism 
of  the  capillaries,  and  as  a  consequence  the  charac- 
teristic lesions  of  the  skin  and  mucous  membrane. 

During  the  secondary  period  the  spirochsetes  are 
found  in  the  papules,  blood,  and  organs. 

It  is  very  difficult  to  find  spirochsetes  in  the  blood 
on  account  of  their  small  numbers. 

In  congenital  syphilis  spirochsetes  are  often  found  in 
large  numbers  in  the  liver,  spleen,  and  lungs.  The 
spirochsetes  are  usually  disposed  around  the  vessels. 
They  are  also  found  in  the  vesicles  of  pemphigus. 
Spirochsetes  have  been  found  in  the  blood,  the  skin 
lesions,  in  the  lymphatic  glands,  in  the  liver,  in  the 
suprarenal  capsules,  in  the  ovaries  or  testicles,  in  the 
lungs,  in  the  spleen,  in  the  pancreas,  in  the  nerves, 
and  in  the  bone  cartilages.  They  are  also  found  in 
the  rachidien  fluid  and  nasal  mucus,  sputum,  ascitic 
fluid,  bile,  urine,  meconium,  and  in  the  gastric  juices. 

Levaditi  and  Roche  quote  nine  instances  of  inocula- 
tion of  syphilis  on  men  by  means  of  syphilitic  blood, 
including  Julien's  two  cases. 


PARASITOLOGY  23 

Hoffmann  was  the  first  to  demonstrate  the  infectivity 
of  blood  obtained  from  patients  in  the  florid  secondary 
stage  of  syphilis  by  inoculation  experiments  on  apes. 
He  showed  that  the  blood  was  infective  before  the 
rash  appeared,  and  remained  so  for  as  long  a  period 
as  six  months  after  the  first  appearance  of  the  disease. 
The  blood,  however,  cannot  contain  any  large  numbers 
of  spirochaetes,  as  only  a  small  percentage  of  experi- 
ments give  positive  results.  The  infectivity  of  the 
spermatic  fluid  of  a  secondary  syphilitic  was  demon- 
strated by  Finger  and  Landsteiner. 

Trinchese  has  reported  his  results  of  the  examination 
of  the  placenta  in  a  hundred  cases  in  which  the  foetus 
was  syphilitic.  He  found  the  results  agreed  with 
those  from  examinations  of  the  foetal  organs,  and 
only  failed  in  one  case  to  find  spirochsetes  in  the 
placenta  when  their  presence  could  be  demonstrated 
in  the  foetal  organs.  They  are,  however,  much  less 
numerous  in  the  placenta  than  in  the  organs.  He 
was  able  to  demonstrate  the  passage  of  the  spirochaeta 
through  the  walls  of  the  villus,  and  he  considers  that 
the  spirochaetae  circulate  in  the  foetal  blood  and  pene- 
trate through  the  vessel  and  villus,  setting  up  a 
nodular  thickening  of  the  syncytium.  The  macro- 
scopic appearance  of  the  placenta  in  these  cases  did 
not  differ  from  that  of  the  normal  placenta.  In  the 
foetal  organs  the  spirochaetes  were  found  in  the  largest 
number  in  the  adrenal  bodies ;  the  liver  and  lungs 
were  the  next  most  infected  organs,  and  here  the 
organism  occurred  most  frequently  in  the  neighbour- 
hood of  the  vessels.  The  ovary,  testicle,  and  epi- 
didymus  almost  constantly  contained  organisms. 


24  SYPHILIS  AND  PARASYPHILIS 

Experimental  inoculations  in  animals  have  proved 
that  blood  in  secondary  syphilis,  semen  in  secondary 
syphilis,  saliva  in  secondary  syphilis,  and  gummata  in 
tertiary  syphilis,  all  contain  the  syphilitic  virus. 

The  occurrence  of  spirochaetae  in  the  semen  is  a 
tardy  proof  of  conceptional  syphilis,  which  was  long 
suspected,  and  appears  to  have  been  clinically  proved 
by  the  case  recorded  by  Buschke  and  Fischer,  in 
which  a  mother,  previously  healthy,  gave  birth  to  a 
syphilitic  child,  and  subsequently  developed  the  disease. 

INOCULATION 

The  first  successful  inoculation  on  animals  was  per- 
formed by  MetchnikofF  and  Roux  on  a  female  chim- 
panzee two  years  old.  The  sites  selected  were  the 
clitoris  and  eyebrow,  and  the  material  used  was  serum 
from  a  human  primary  sore.  After  about  twenty-six 
days  a  chancre  developed  on  the  clitoris,  and  a  papular 
rash  occurred  a  month  after  the  appearance  of  the 
chancre. 

MetchnikofF  and  Roux  have  since  reported  the 
development  of  a  secondary  rash  in  60  per  cent,  of 
animals  whose  inoculation  was  followed  by  a  primary 
sore,  and  that  this  rash  usually  commences  thirty-three 
days  after  the  first  appearance  of  the  chancre.  In  the 
chimpanzee  the  rashes  can  be  seen  on  the  skin  of  the 
head,  back,  and  abdomen,  and  are  usually  either  papular 
or  macular.  Mucous  plaques  also  are  found  on  the 
mucous  membranes. 

The  lower  monkeys  can  also  be  successfully  inocu- 
lated, and  a  chancre  produced,  but  there  is  not  such 


PARASITOLOGY  25 

a  large  percentage  of  successful  inoculations,  and 
secondary  symptoms  seldom,  if  ever,  occur. 

Bertarelli  was  the  first  experimenter  to  obtain  satis- 
factory results  with  rabbits.  He  inoculated  the  cornea, 
and  a  well-marked  keratitis  was  produced,  which  com- 
menced four  weeks  after  inoculation.  The  lesion  first 
appeared  as  a  greyish  opacity,  accompanied  by  some 
injection  of  the  ciHary  vessels.  The  opacity  increases 
in  size  until  half  the  cornea  may  be  affected,  and  later 
the  bloodvessels  grow  in  from  the  sclerotic.  The 
lesion  tends  to  heal  spontaneously,  and  in  a  couple  of 
months  or  so  recovery  usually  takes  place. 

Parodi  later  was  successful  in  inoculating  rabbits  in 
the  testicle.  He  introduced  the  virus  into  the  sub- 
tance  of  the  testicle,  but  Truffi  soon  afterwards  was 
able  to  show  that  it  was  sufficient  to  introduce  the 
virus  under  the  skin  covering  the  testicle.  When 
transmitting  the  infection,  some  observers  use  the 
serum  obtained  in  a  similar  way  to  that  required  for 
examination  by  dark-ground  illumination,  which  has 
already  been  described  ;  others  use  the  fluid  obtained 
from  the  inside  of  an  infected  testicle,  and  others 
transplant  small  pieces  of  the  lesion  containing  spiro- 
chastes. 

One  of  two  techniques  is  usually  employed  for  the 
inoculation.  In  the  first  the  epithelial  layers  of  the 
skin  are  scarified  with  a  scalpel,  and  the  virus  then 
rubbed  in,  the  procedure  being  similar  to  that  of 
ordinary  vaccination  with  calf-lymph.  Finger  and 
Landsteiner  introduced  the  second,  or  subepidermal 
technique.  Here  the  epithelium  is  deeply  scarified, 
and  the  virus  rubbed  and  pushed  into  the  deeper 
layers  of  the  skin. 


26  SYPHILIS  AND  PARASYPHILIS 

With  a  primary  inoculation,  in  from  five  to  eight 
weeks  a  small  nodule  occurs  in  the  skin,  which 
gradually  increases  in  dimensions  up  to  about  the  size 
of  a  pea,  which  may  or  may  not  ulcerate.  Occasionally, 
infiltration  of  the  skin  takes  the  place  of  a  definite 
nodule. 

If  the  testicular  substance  is  involved,  the  testicle 
will  become  enlarged,  hard,  and  nodular. 

Repeated  passages  apparently  increase  the  virulence 
for  the  species,  as  the  incubation  period  is  shortened, 
even  to  as  little  as  a  fortnight,  and  a  far  higher  per- 
centage of  successful  inoculations  are  recorded,  even 
up  to  80  or  90  per  cent. 

The  infection  in  rabbits  is  nearly  always  a  local  one. 
Repeated  rabbit  passages  do  not  apparently  increase 
the  virulence  of  the  spirochaete  for  apes. 

Roux,  MetchnikofF,  Levaditi,  and  Roche,  of  the 
Pasteur  Institute,  have  elicited  many  interesting  facts 
bearing  on  the  pathology  of  syphilis,  by  means  of 
inoculation  experiments  on  the  higher  apes.  They 
found  that  a  small  effusion  of  blood  or  serum  facilitates 
the  penetration  of  the  virus,  that  a  larger  haemorrhage 
prevents  successful  inoculation,  and  that  the  most 
constant  results  were  obtained  with  superficial  scarifica- 
tion of  the  epidermis.  The  spirochaetes  were  found 
to  be  easily  destroyed  by  phagocytes,  and  were  seen 
inside  the  macrophages  and  polymorphonuclears  in 
the  lungs,  liver,  and  spleen  of  new-born  congenital 
syphilitics.  Neisser,  in  fifty-one  cases  of  subcutaneous 
injection,  did  not  obtain  one  positive  result.  Thirty- 
three  of  these  cases  showed  themselves  later  sensitive 
to  inoculation  by  the  epidermis,  and  certain  of  these 


PARASITOLOGY  27 

which  resisted  the  first  scarification  reacted  to  the 
second.  Thirteen  were  immune  to  all  methods  of 
inoculation,  probably  due  to  natural  immunity,  and 
not  to  the  fact  that  the  subcutaneous  inoculation  had 
'  taken.'  Probably  the  subcutaneous  inoculations  excite 
a  greater  leucocytosis  than  inoculation  of  the  super- 
ficial layers  of  the  skin,  with  the  result  that  the  spiro- 
chaetes  are  destroyed.  Intravenous  or  intraperitoneal 
inoculation  gave  no  positive  results ;  inoculation  into 
a  lymphatic  gland  was  also  negative.  Inoculation 
into  testicles  was  followed  in  one  case  by  a  general 
immunity  without  local  lesion,  and  in  a  second  the 
spirochsete  was  found  in  the  bone-marrow  of  an  animal 
killed  fifty-six  days  after  the  inoculation.  The  general 
opinion  of  experimenters  seems  to  be  that  the  spiro- 
chaeta  is  incapable  of  effecting  an  entrance  through 
sound  skin  or  mucous  membrane,  and  if  their  results 
are  correct  the  great  importance  and  danger  of  little 
superficial  erosions  and  abrasions  are  emphasized. 

J.  Hutchinson,  junior,  expresses  the  firm  belief  in 
the  frequent  passage  of  the  syphilitic  virus  through 
unabraded  or  normal  skin  and  mucous  membrane. 

Positive  inoculations  were  obtained  in  orang-outangs 
(not  in  other  apes)  with  material  from  bone-marrow 
and  spleen,  and  much  less  frequently  with  material 
from  the  testicle  and  lymphatic  glands,  thus  showing  a 
marked  preference  for  blood-forming  tissues.  Negative 
results  were  obtained  with  inoculation  with  material 
from  broken-down  gummata,  but  with  unbroken  gum- 
mata  that  were  opened  and  scraped,  and  the  evacuated 
material  ground  up  and  inoculated,  chancres  developed 
in  60  per  cent,  of  cases. 


28  SYPHILIS  AND  PARASYPHILIS 

In  man  seven  positive  results  were  obtained  out  of 
eighteen  cases  inoculated  with  blood  taken  from  cases 
with  marked  secondary  syphilis. 

Spermatozoa  may  occasionally  contain  the  virus ; 
inoculations  with  milk  have  so  far  all  proved  negative, 
and  cerebro-spinal  fluid  has  only  very  rarely  given  a 
positive  result. 

Filtering  destroys  the  power  of  the  virus  as  estimated 
by  inoculation.  The  virus  may  be  sterilized  by  desic- 
cation, by  keeping  for  three  hours  at  a  temperature  of 
io°  C,  or  half  an  hour  at  48°  C,  or  subjecting  it  to 
the  rays  of  the  uveal  lamp  or  the  X  rays.  After 
twenty-two  passages  through  apes  the  virus  becomes 
attenuated,  and  the  period  of  incubation  lessened  from 
nineteen  to  seven  days. 

Levaditi  and  Roche,  in  their  book,  '  La  Syphilis,' 
mention  the  case  of  a  man,  aged  seventy-nine,  who 
was  inoculated  with  a  virus  attenuated  by  passage 
through  several  apes,  and  who  developed  small  papules 
at  the  point  of  the  inoculation  ;  but  no  ulceration  of  the 
papules  occurred,  nor  any  secondary  symptoms. 

INCUBATION  PERIOD 

It  has  been  observed  that  the  more  resistant  the 
animal  is  to  infection,  the  shorter  is  the  incubation 
period.  Neisser  considers  that  the  duration  of  in- 
cubation depends,  not  on  the  virulence  of  the  organism, 
nor  on  the  resistance  of  the  individual,  but  only  on 
the  quantity  of  virus  introduced.  Levaditi,  on  the 
other  hand,  considers  that  resistance  and  virulence 
both  play  an  important  part.    Of  six  animals  in  which 


PARASITOLOGY  29 

the  scarified  spots  were  excised  ten  minutes,  twenty 
minutes,  two  hours^  four  hours,  ten  hours,  and  twelve 
hours  after,  no  subsequent  lesion  appeared.  In  another 
experiment,  when  the  points  of  inoculation  were 
excised  eight  and  fourteen  hours  after  scarification, 
chancres  appeared.  The  duration  of  the  period  of 
incubation  is  due  to  the  slowness  of  multiplication 
of  spirochaetae  transplanted  into  new  surroundings. 
Already,  long  before  the  appearance  of  the  chancre, 
the  virus  has  reached  the  circulation.  The  organism 
spreads  by  the  blood,  and,  perhaps  by  preference,  by 
the  lymphatics. 

REINFECTION 

There  appears  to  be  conclusive  evidence  that  no 
individual  is  immune  to  syphilis,  or  that  a  syphilitic 
infection  confers  immunity.  Numerous  well-authen- 
ticated cases  are  now  reported  of  reinfection  with 
syphilis,  and  if  an  individual  is  immune  to  syphilis,  we 
may  conclude  that  he  is  still  infected  with  it. 

Cases  of  tabes  and  general  paralysis  have  been 
inoculated  without  success. 

J.  Hutchinson,  junior,  has  shown  that  the  interval 
between  two  attacks  of  syphilis  may  be  so  short  a 
time  as  eighteen  months,  and  that  the  second  attack 
may  be  either  slighter  or  more  severe  than  the  first. 
Nothing  positive  can  be  laid  down  on  this  point. 

J.  Hutchinson,  senior,  has  recorded  one  definite 
example  of  a  patient  having  three  attacks  of  syphilis. 

Only  a  small  number  of  undoubted  cases  have  been 
recorded  of  the  development  of  acquired  syphilis  in 


30  SYPHILIS  AND  PARASYPHILIS 

congenital  syphilitics,  and  J.  Hutchinson,  junior, 
doubts  whether  he  has  seen  more  than  three  or  four 
in  twenty  years'  very  extensive  experience. 

Since  the  introduction  of  salvarsan  several  cases  of 
reinfection  within  a  few  months  are  recorded,  and 
successful  reinfection  has  been  performed  on  a  chim- 
panzee with  only  three  months'  interval  between  the 
two  inoculations,  salvarsan  having  been  administered 
after  the  appearance  of  a  chancre  had  demonstrated 
that  the  first  inoculation  was  successful. 

The  immunity  to  superinfection  produced  by  the 
presence  of  syphilitic  infection  is  not  developed  at 
once,  and  is  not  absolute. 

Metchnikoff  and  Roux  obtained  positive  reinocula- 
tions  in  monkeys  ten  days  after  the  primary  chancre 
had  appeared. 

Finger  and  Landsteiner  could  not  obtain  inocula 
tions  after  the  chancre  had  been  present  for  more 
than  five  days. 

Neisser  obtained  seventeen  positive  results  in  fifty 
reinoculations  on  apes ;  of  these,  eight  were  made  on 
the  appearance  of  the  primary  sore,  and  nine  later. 

Positive  results  have  been  obtained  when  the  second 
inoculation  was  made  as  late  as  fifty  days  after  the 
appearance  of  the  primary  sore. 

In  the  secondary  stage  of  syphilis  there  is  usually, 
but  not  invariably,  complete  immunity  to  super- 
infection, and  this  is  also  true  of  tertiary  syphilis. 
This  pseudo-immunity  disappears  with  cure. 

Frage  and  Landsteiner  have  succeeded  in  obtaining 
reinfection  in  the  primary  period  and  in  the  secondary 
and  tertiary  periods.    According  to  their  observations. 


PARASITOLOGY  31 

reinfection  was  expressed  by  a  sclerosis  in  the  primary 
period,  by  papules  in  the  secondary  period,  and  by 
gummas  in  the  tertiary  period. 

The  sequence  of  events  in  syphilis,  which  has  been 
roughly  divided  into  primary,  secondary,  and  tertiary 
syphilis  and  parasyphilis,  is  capable  of  two  explana- 
tions :  (i)  That  the  Spivochceta  pallida  undergoes  a 
series  of  changes  when  resident  in  the  tissues,  and 
that  in  each  of  these  successive  phases  the  symptoms 
to  which  it  can  give  rise  are  peculiar  to  the  stage  at 
which  it  has  arrived  ;  (2)  that  it  is  the  tissues  which 
change,  so  that  the  longer  the  spirochaete  acts  on 
them,  the  more  the  lesions  which  result  from  any 
increased  activity  of  this  parasite  approach  first  the 
characters  peculiar  to  the  so-called  secondary,  and 
then  those  of  the  tertiary,  stage. 

The  first  explanation  would  be  difficult  to  prove, 
and  against  it  is  the  fact  that  infection  with  spiro- 
chaetes  derived  from  a  secondary  or  tertiary  lesion 
results  in  a  primary  sore.  In  favour  of  the  second 
explanation  is  the  well-known  fact  that  in  the  majority 
of  cases  of  syphilis,  whether  untreated  or  treated  with 
mercury,  reinoculation  does  not  result  in  the  produc- 
tion of  a  second  chancre.  As  Queyrat  showed,  this 
refractory  behaviour  of  the  skin  and  mucous  mem- 
branes to  infection  from  without  is  gradually  developed 
during  the  ten  days  which  succeed  the  appearance  of 
the  primary  sore  ;  as  the  end  of  the  period  approaches, 
the  sore  resulting  from  reinoculation  becomes  more 
and  more  evanescent  till,  finally,  no  chancre  follows. 
Finger  and  Landsteiner  succeeded  in  producing  skin 
lesions  in  such  cases  by  inserting  large  amounts  of 


32  SYPHILIS  AND  PARASYPHILIS 

syphilitic  virus  in  pockets  under  the  epidermis ;  these 
were  not  chancres,  however,  but  simulated  the  lesions 
from  which  the  patient  was  suffering  at  the  time. 
Thus  in  the  secondary  stage  a  papule  followed  the 
inoculation,  while  in  patients  suffering  from  guramata 
or  ulcerating  syphilides  identical  lesions  formed  at  the 
sites  of  inoculation.  That  these  were  due  to  the  newly 
introduced  spirochaetes,  and  not  to  those  already 
infecting  the  patients,  was  shown  by  the  fact  that, 
if  the  former  were  previously  killed,  the  result  of  the 
inoculation  was  negative. 

The  evidence  is,  therefore,  strongly  in  favour  of  the 
theory  that  it  is  the  length  of  time  during  which  the 
spirochaetes  have  acted  on  the  tissues  which  determines 
the  characters  of  the  successive  manifestations  of 
syphilis. 

Neisser  argues  that  a  really  cured  syphilis  does  not 
leave  behind  it  a  state  of  immunity,  but  thinks,  on 
the  contrary,  that  only  in  those  cases  in  which  the 
disease  was  still  present  was  there  a  kind  of  so-called 
immunity — that  is  to  say,  a  resistance  to  a  fresh 
inoculation.  He  cannot  accept  the  old  dogma  that 
during  the  presence  of  syphilis  an  absolute  prevention 
against  new  inoculation  exists,  but  neither  can  he 
agree  with  the  opinion  of  Finger,  Ehrmann,  and  others, 
who  regard  super-infection  as  quite  a  usual  occurrence. 
He,  Neisser,  believes  that  we  must  accept  the  state- 
ment that,  especially  during  the  first  few  years  of  the 
disease,  as  long  as  the  virus  of  syphilis  still  remains 
in  the  body,  there  exists  a  nearly  complete  resistance 
to  a  second  infection. 

Doubtless  in  the  future   many  more  cases  of  re- 


PARASITOLOGY  33 

infection  will  occur,  since  modern  methods  of  treat- 
ment will  probably  succeed  in  rapidly  effecting  a  cure 
of  syphilis  in  many  instances. 

The  old  supposition  is  thoroughly  false  which  states 
that  a  person  with  syphilis,  or  one  who  has  had 
syphilis,  can  run  the  risk  of  acquiring  further  infection 
without  fear  of  penalty. 

IMMUNITY 

The  susceptibility  of  individuals  with  regard  to 
syphilis  depends  on  the  degree  of  their  immunity, 
either  natural  or  acquired.  Certain  races  have  up 
till  now  been  considered  but  little  susceptible  to  its 
infection,  as,  for  example,  the  inhabitants  of  Iceland, 
Greenland,  and  Central  Africa.  It  is  now  recognized, 
however,  that  this  immunity  is  only  apparent,  as,  since 
intimate  relations  with  Europeans  were  established, 
syphilis  has  appeared. 

The  question  of  immunity  in  the  descendants  of 
families  of  a  syphilitic  taint  cannot  be  considered  as 
proved.  The  only  certain  proof  is  the  resistance  to 
inoculation,  and  it  is  evidently  impossible  to  state 
whether  the  absence  of  infection  after  coitus  with  an 
individual  showing  infective  lesions  has  been  due  to 
the  integrity  of  the  mucous  membrane  or  not. 

The  rarity  of  cases  of  reinfection  has  long  been 
considered  proof  of  an  acquired  immunity.  There 
is,  however,  a  possibility  of  reinfection.  Since  the 
Congress  in  London  in  1896,  many  reliable  observers 
have  published  cases  of  reinfection. 

Numerous  works  on  the  serum  therapy  of  syphilis 

3 


34  SYPHILIS  AND  PARASYPHILIS 

have  shown  that  the  serum  is  capable  of  producing 
some  effect,  but  the  problem  cannot  be  solved  until 
we  are  able  to  obtain  a  very  active  animal  serum. 

The  possibility  of  active  immunization  of  animals 
against  syphilitic  virus  was  shown  for  the  first  time 
by  Roux  and  Metchnikoff,  who  employed  a  virus 
attenuated  by  several  passages  through  macaques. 
They  considered  that  the  slight  form  of  the  disease 
produced  by  such  an  inoculation  prevents  an  infection 
following  an  inoculation  with  non-attenuated  virus. 

Metchnikoff  has  satisfied  himself  by  experiments  on 
macaques  that  attenuation  is  obtained  by  passage. 
Only  local  lesions  occurred  in  which  the  spirochaetes 
were  found,  and  general  symptoms  did  not  appear. 

Metchnikoff  and  Neisser  have  tried  to  obtain  passive 
immunity  with  the  help  of  serum  from  monkeys  who 
have  recovered  from  infection.  Satisfactory  results, 
however,  have  not  been  achieved,  and  the  monkeys 
were  not  guarded  against  subsequent  infection.  They 
have  also  vainly  tried  to  obtain  an  immune  serum 
from  the  goat,  injected  with  material  very  rich  in 
spirochsetes. 

In  the  hope  of  provoking  an  active  immunity  in 
cases  of  primary  syphilis,  and  with  a  view  to  prevent 
the  occurrence  of  secondary  syphilis,  Kraus  and  Volk 
inoculated  with  a  carbolized  emulsion  of  syphilitic 
lesions ;  they  consider  that  they  have  abated  the 
disease  in  a  few  instances. 

For  the  active  immunization  of  monkeys,  emulsions 
have  been  tried  made  with  the  glands  corresponding 
to  the  chancre,  and  also  with  organs  of  congenital 
syphilitics  containing  large  numbers  of  spirochaetes. 


PARASITOLOGY  35 

These  emulsions  were  cooled  in  the  ice-chest,  and 
carbolic  acid  added  in  a  dilution  of  0*5  per  cent. 
Repeated  inoculations  of  the  same  product  have  not 
produced  immunization  of  animals. 

If,  also,  the  degree  of  immunity  of  the  organism  is 
not  very  high,  it  will  manifest  itself  by  the  presence 
in  the  blood  and  in  the  organs  of  specific  antibodies, 
the  formation  of  which  corresponds  usually  with  the 
elaboration  of  immunity.  These  antibodies  are  repre- 
sented by  agglutinins,  bacteriolysins,  precipitins,  and  a 
specific  body  producing  the  fixation  of  complement. 
The  agglutinins  are  formed  after  appearance  of  the 
primary  chancre. 

Effect  of  Treatment  on  the  Spirochaeta.— 
Salvarsan,  especially  if  given  intravenously  and  in 
efficient  dosage,  causes  a  very  rapid  disappearance  of 
the  spirochaetae,  which  usually  cannot  be  found  after 
twenty-four  hours,  and  can  practically  never  be 
demonstrated  after  three  days. 

Mcintosh  and  Fildes  have  recorded  an  experiment 
to  show  the  relative  merits  of  salvarsan  and  mercury. 
They  selected  two  rabbits  with  severe  testicular 
syphilitic  lesions,  and  injected  one  intravenously  with 
o'l  gramme  of  salvarsan,  and  gave  the  other  two  doses 
of  biniodide  of  mercury  intravenously,  giving  in  all 
0-02  gramme  of  biniodide.  No  spirochaetes  could  be 
found  in  the  salvarsan-treated  rabbit  after  seven  hours, 
while  they  persisted  in  the  mercury-treated  rabbit  for 
four  days. 

Metchnikoff  and  Roux  have  found  that  a  chimpanzee, 
inoculated  with  virus  and  the  part  rubbed  for  ten 
minutes  with  calomel  ointment  three-quarters  of  an 


36  SYPHILIS  AND  PARASYPHILIS 

hour  after  inoculation,  developed  no  signs  of  syphilis, 
and  showed  itself  sensitive  to  subsequent  inoculations. 
A  medical  student,  inoculated  with  the  virus  and 
rubbed  with  calomel  ointment  for  five  minutes  one 
hour  after  inoculation,  developed  no  signs  of  syphiHs ; 
but  an  unrubbed  monkey  and  a  monkey  rubbed  twenty- 
four  hours  after  inoculation  both  developed  syphilis. 


CHAPTER  III 
SYPHILITIC  ANiEMIAS 

Anemia  has  been  recognized  for  a  long  time  as  often 
associated  with  syphilis,  and  it  can  be  looked  upon  as 
probably  the  most  constant  of  the  constitutional 
changes  of  this  disease,  and  is  especially  noticeable  in 
the  secondary  stage. 

In  1869  Virchow  demonstrated  a  leucocytosis 
coincident  with  the  enlargement  of  the  lymphatic 
glands,  with  a  relative  increase  in  the  number  of 
lymphocytes.  Zehleneff  examined  the  blood  of  twenty 
patients  daily  for  several  weeks,  and  found  a  lympho- 
cytosis in  seventeen. 

In  1872  Molassi  first  demonstrated  the  existence  of 
a  pronounced  decrease  in  the  number  of  red  cells  in 
three  infected  wet  -  nurses,  and  considered  that  the 
anaemia  coincided  with  the  general  manifestations  of 
the  disease. 

In  1874  Wilbowcheivitch  demonstrated  a  reduction 
in  the  number  of  red  corpuscles  in  the  primary  period 
coincident  with  an  increase  in  the  leucocytes.  Outre 
noticed  the  appearance  of  large  nucleated  red  cells 
(megaloblasts)  during  the  appearance  of  the  anaemia, 
and  small  nucleated  red  cells  (microblasts)  at  the  end 

37 


38  SYPHILIS  AND  PARASYPHILIS 

of  this  period.  Gram  considers  that  there  is  an  increase 
in  the  number  of  microcytes,  and  that  red  cells  of  an 
irregular  shape  (poikilocytes)  are  always  present. 

Marie  has  recorded  that  the  red  cells  show  a 
diminished  resistance  to  cold,  so  that  they  become 
laked  when  placed  on  ice  more  easily  than  normal 
cells. 

The  leucocytosis  does  not  usually  go  above  15,000 
to  18,000  per  c.mm.,  but  it  is  an  early  and  very 
constant  symptom  and  lasts  for  a  long  time,  so  that 
often  it  is  the  first  and  last  syphilitic  abnormality  of 
the  blood  which  is  recorded.  It  commences  indepen- 
dently of  any  local  inflammatory  or  erosive  condition 
of  the  skin  or  mucous  membrame,  and  usually  occurs 
between  the  healing  of  the  chancre  and  appearance  of 
the  rash. 

Most  authors  agree  that  ansemia  reaches  its  climax 
during  the  secondary  period,  but  different  authorities 
vary  as  to  the  exact  time  of  its  onset,  some  stating  that 
it  precedes  the  rash,  and  others  that  it  coincides  with 
or  follows  it. 

A  lymphocytosis  is  usually  first  noticed,  to  be 
followed  later  by  a  diminution  of  haemoglobin  and 
in  the  number  of  the  red  cells.  All  these  factors  have 
been  noticed  three  weeks  before  the  appearance  of 
the  rash.  After  the  appearance  of  the  rash  the 
anaemia  grows  worse,  and  tends  to  run  a  parallel 
course  with  the  clinical  manifestations,  becoming 
intense  with  malignant  syphilis,  or  passing  off  as  the 
symptoms  clear  up. 

In  certain  cases,  coincident  with  the  amelioration  of 
the  anaemia,  there  is  an  increase  of  nucleated  reds  and 


SYPHILITIC  AN  MM  IAS  39 

blood  platelets.  The  oscillations  in  the  condition  of 
the  blood  can  therefore  give  an  index  of  the  resistance 
of  the  individual  to  infection. 

In  latent  syphilis  with  no  clinical  manifestations,  an 
anaemia  may  be  the  only  symptom  besides  the  Wasser- 
mann  reaction,  which  shows  that  the  cure  is  not  com- 
plete and  permanent.  Sometimes,  however,  though 
the  blood  appears  to  have  become  completely  normal, 
the  anaemia  returns  with  a  reappearance  of  symptoms. 

The  rise  and  fall  in  the  amount  of  haemoglobin  is 
coincident  with  the  increase  and  decrease  in  the 
number  of  lymphocytes,  and  Mott  considers  that  this 
may  indicate  that,  with  the  pouring  out  of  an  abundance 
of  lymphocytes  from  the  lymph-stream  into  the  blood- 
stream, there  was  associated  a  pouring  out  of  the 
virus,  causing  the  irritation  and  hyperplasia  of  the 
lymph-cell  elements.  He  considers  that  the  anaemia 
may  be  due  to  interference  with  the  functions  of  the 
blood-forming  tissues.  In  support  of  this  is  the  fact, 
established  experimentally  by  Neisser,  that  the  red 
marrow  and  spleen  are  especially  rich  in  the  virus. 
Since  mercury  rapidly  improves  the  anaemia,  Mott 
thinks  it  probable  that  it  does  so  by  arresting  the 
development  of  the  spirochaetes  in  the  blood-forming 
tissues. 

The  anaemia  seems  to  have  a  particular  predilection 
for  w^omen  and  weak  and  over-worked  young  people, 
and  seems  to  be  usually  of  the  nature  of  a  chlorosis. 
This,  however,  is  not  invariable,  and  syphilis  may 
produce  alterations  of  the  most  different  kinds  in  the 
blood,  and  the  blood-picture  may  not  be  characteristic 
of  any  particular  clinical  form  of  anaemia.    Though  the 


40  SYPHILIS  AND  PARASYPHILIS 

early  stages  almost  invariably  show  the  anaemia  of  a 
chlorotic  type,  later  on  the  appearance  may  be  that  of 
pernicious  anaemia. 

In  late  syphilis  the  blood  is  usually  very  nearly 
normal,  but  really  severe  anaemia,  when  it  occurs  in 
syphilis,  does  so  only  in  the  later  stages. 

The  cause  of  this  occasional  appearance  of  grave 
anaemia  is  unknown. 

That  the  anaemia  is  not  due  to  the  mercury  taken  as 
treatment  is  shown  by  the  fact  that  it  exists  prior  to 
mercurial  treatment,  and  that  the  blood  condition 
improves  under  treatment.  It  is  only  when  mercury 
has  been  given  for  a  long  time  that  its  deleterious 
effect  upon  the  blood  is  shown. 

Dominici  divides  syphilitic  anaemias  into  three 
classes  : 

1.  Chlorotic  type,  without  leucocytosis. 

2.  ,,  ,,       with  leucocytosis. 

3.  Pernicious  type. 

Chlorotic  Type,  without  Leucocytosis  : 

Twelve  days  before  rash . 

Red  cells   ...  ...  ...     5,350,000. 

Haemoglobin  ...  ...     100  per  cent. 

Leucocytes  ...  ...     5,000. 

Twelve  days  after  rash. 

Red  cells  ...  ...  ...     3,950,000. 

Haemoglobin  ...  ...     80  per  cent. 

Leucocytes  ...  ...     8,000. 

Chlorotic  Type,  with  Leucocytosis  : 

Red  cells  ...  ...  ...  4,300,000. 

Haemoglobin  ...  ...  75  per  cent. 

Leucocytes  ...  ...  12,200. 

Colour  index  ...  ...  0*87. 


SYPHILITIC  ANEMIAS  41 

Pernicious  Type : 

Red  cells  ...  ...  ...     1,540,000. 

Haemoglobin  ...  ...     40  per  cent. 

Colour  index  ...  ...     1-33. 

Influence  of  Treatment  on  Syphilitic  Anaemia. 

Justus  states  that  when  a  large  inunction  or  injection 
of  mercury  is  given  before  the  rash  appears,  but  not 
before  the  time  when  the  general  enlargement  of  the 
lymphatic  glands  shows  that  the  toxin  is  disseminated 
throughout  the  body,  the  treatment  is  followed  by  an 
immediate  decrease  in  the  percentage  of  haemoglobin, 
from  10  to  20  per  cent.,  to  be  followed  by  a  rise,  even 
above  normal,  in  a  few  days.  This  fall  followed 
by  a  rise  is  so  constant  that  it  can  be  used  as  a 
reliable  test  for  the  presence  of  syphilitic  infection. 
Justus  considers  that  this  drop  in  the  amount  of 
haemoglobin,  which  is  both  rapid  and  considerable,  is 
a  specific  test  for  a  case  of  florid  syphilis,  and  may  be 
obtained  in  any  form  of  syphilis — late  primary, 
secondary,  tertiary,  or  hereditary — provided  the  disease 
be  at  that  time  florid,  and  not  when  or  just  before  the 
symptoms  begin  to  recede.  It  may  again  be  obtained 
in  cases  of  relapse  and  until  the  relapse  has  passed  its 
climax.  It  is  not  present  during  the  primary  stage  so 
long  as  the  infection  is  limited  to  the  chancre  and  its 
neighbouring  glands,  but  only  after  the  toxin  has 
become  widespread,  as  shown  by  the  enlargement  of 
distant  glands.  Justus's  claim  that  this  test  is  pathog- 
nomic cannot  be  taken  as  proved,  though  it  is 
undoubtedly  present  in  a  large  percentage  of  cases. 
Iron  has  no,  or  but  a  slight  and  transient,  influence  on 
syphilitic  anaemia. 


42  SYPHILIS  AND  PARASYPHILIS 

Syphilitic  Anaemias  of  Infancy. 

The  form  of  anaemia  occurring  in  congenital  syphilitic 
children  may  be  divided  into  three  classes  : 

1.  Chloro-anaemia  with  Leucocytosis,  in  which 
the  number  of  red  cells  may  be  normal,  and  the  hgemo- 
globin  greatly  reduced  with  a  moderate  leucocytosis. 
The  following  example  is  from  a  child  of  ten  months  : 

Red  cells  ...  ...  ...  4,637,000. 

Haemoglobin  ...  ...  35  per  cent. 

Leucocytes  ...  ..  17,880. 

Colour  index  ...  ...  0*38. 

2.  Pernicious  Type,  where  the  red  cells  are  greatly 
diminished  in  number,  and,  although  the  haemoglobin 
is  reduced  also,  it  is  not  so  to  such  an  extent  as  the 
red  cells,  and  therefore  the  colour  index  is  raised.  In 
this  type  there  is  but  slight  leucocytosis^  if  any. 
Example : 

Red  cells  ...  ...  ...  1,236,000. 

Haemoglobin  ...  ...  30  per  cent. 

Leucocytes  ...  ...  11,700. 

Colour  index  ...  ...  i'25. 

In  this  type  there  are  usually  very  few  nucleated  red 
cells,  but  large  numbers  of  megalocytes  and  giganto- 
cytes. 

3.  LeucaemicType. — Here  the  leucocytes  may  reach 
very  large  numbers  and  almost  present  the  appearance 
of  a  myologenous  leucaemia.  The  combined  count 
of  lymphocytes,  myelocytes,  and  polymorphonuclears 
may  number  50,000  or  more.  This  type  usually  shows 
a  large  number  of  nucleated  reds,  many  of  these 
showing  division  of  the  nucleus. 


SYPHILITIC  ANMMIAS  43 

Drysdale  and  Thursfield  consider  the  following  blood- 
count  typical  of  ordinary  congenital  syphilis  : 


Red  cells  ... 

...     4,224,000. 

Haemoglobin 

...     76  per  cent 

Leucocytes 

...     13,463. 

Colour  index 

...     0-9. 

Mott  considers  that  there  is  nothing  in  most  cases 
of  hereditary  syphilis  which  is  in  any  way  remarkable 
or  different  from  w^hat  may  be  seen  in  any  moderate 
secondary  anaemia  in  infancy.  He  considers  that  it  is 
impossible  to  lay  very  much  stress  on  the  importance 
of  lymphocytosis,  as  this  is  an  hereditary  feature  of  all 
infantile  anaemias,  and  he  considers  it  impossible  to 
name  any  one  feature  in  the  blood-count  which  is 
distinctive  of  syphilis. 

Following  mercurial  treatment  there  is  often  a  fall 
in  the  number  of  cells  coincident  sometimes  with 
haemoglobinuria,  owing  to  the  destruction  of  those  red 
cells  which  have  been  weakened  by  the  syphilitic 
toxin.  If  the  treatment  is  carried  too  far  it  may  then 
be  the  cause  of  an  anaemia. 

It  has  been  suggested  that  as  cases  of  spasmodic 
haematuria  practically  always  show  a  syphilitic  history, 
the  blood  of  syphilitics  contains  a  haemolysin.  The 
author  has  examined  the  serum  of  twenty-five  cases  of 
syphilis,  and  has  been  unable  to  find  any  trace  of  such 
haemolysin. 

Primary  Syphilis. — No  blood  change  is  noticed 
during  this  period,  the  first  alteration  usually  appearing 
during  the  healing  of  the  chancre  a  fortnight  or  three 
weeks  before  the  onset  of  any  secondary  manifestations. 
Probably  the  first  change  is  that  of  a  leucocytosis  with 


44  SYPHILIS  AND  PARASYPHILIS 

a  relative  and  absolute  increase  of  lymphocytes.  A 
slight  deficiency  in  haemoglobin  then  follows,  to  be 
followed  again  a  little  later  by  a  decrease  in  the  number 
of  red  cells. 

Secondary  Syphilis. — The  red  cells  drop  very 
rapidly,  about  200,000  a  day,  and  in  untreated  cases 
may  fall  to  2,000,000 ;  at  the  same  time  the  quantity 
of  haemoglobin  decreases.  The  red  cells  are  pale  and 
vary  in  size  and  shape,  showing  a  diminished  resistance 
to  cold.  The  leucocytes  average  12,000  to  16,000,  and 
may  reach  25,000.  At  this  stage  the  increase  is  both 
of  polymorphonuclears  and  lymphocytes,  and  later 
there  may  be  a  slight  eosinophilia. 

Leoper  thinks  that  the  polymorphonuclear  leuco- 
cytes appear  with  each  exacerbation  of  the  symptoms, 
and  that  the  lymphocytes  appear  in  the  intervals 
between  such  exacerbations,  when  there  may  be  a 
diminution  in  the  number  of  polymorphonuclear  leuco- 
cytes. Nucleated  red  cells  appear  to  increase  with 
the  amelioration  of  the  symptoms. 

Mast  cells  may  be  numerous  or  may  appear  only 
occasionally. 

Most  observers  agree  that  there  is  an  increase  in 
the  amount  of  albumin  in  the  serum  in  secondary 
syphilis.  This  was  first  observed  by  Aparis  in  1840, 
who  reported  that  the  albumin  of  the  plasma  was 
increased  proportionately  with  the  decrease  of  red 
blood  cells,  the  fibrin  and  serum  being  still  of  normal 
proportions.  Gram  later  confirmed  the  increase  in 
the  amount  of  albumin. 

In  1896  Valerio  noticed  a  decrease  in  the  alkalinity, 
density,  and  the  amount  of   chlorides  present  in  the 


SYPHILITIC  ANMMIAS  45 

serum,  and,  proportional  to  the  destruction  of  the  red 
cells,  there  must  be  an  increase  in  pigment,  potassium 
salts,  and  phosphoric  acid. 

Tertiary  Syphilis. — There  is  generally  little  blood- 
change  at  this  stage,  although,  as  stated  above,  very 
severe  anaemias,  when  they  occur,  usually  are  found 
during  this  stage.  As  a  rule,  there  is  a  slight  increase 
in  the  number  of  leucocytes  from  9,000  to  13,000,  but 
sometimes  the  leucocytes  are  less  than  the  normal 
(leucopeny).  The  increase  may  be  either  in  the  poly- 
morphonuclears or  lymphocytes.  Some  observers  state 
that  eosinophiles  are  present  in  greater  numbers  in 
this  than  in  other  stages. 

During  the  tertiary  stage  with  severe  anaemia  there 
is  usually  leucocytosis  with  a  high  lymphocytosis, 
myelocytes  also  being  present.  A  marked  leucocytosis 
is  an  aid  in  excluding  pernicious  anaemia.  In  an  adult 
high  lymphocytosis  and  an  increase  in  eosinophiles 
suggest  syphilis,  and  in  a  child  this  blood-picture 
might  suggest  rickets  also.  A  low  haemoglobin  per- 
centage and  a  high  percentage  of  small  mononuclears 
have  been  considered  indications  that  the  infection  is 
acute. 

Parasyphilis. — Tabes.— In  tabes  there  is  but  little 
change;  perhaps  there  may  be  a  slight  excess  of 
polymorphonuclears. 

General  Paralysis, — In  G.P.I,  the  blood-changes  are 
not  very  constant ;  sometimes  there  is  an  increase 
in  the  number  either  of  polymorphs  or  lymphocytes ; 
sometimes  there  is  an  increase  in  the  eosinophiles,  and 
sometimes  the  white  count  is  normal. 


CHAPTER  IV 

THEORIES     FOR     AND      NATURE     OF 
WASSERMANN  REACTION. 

Pfeiffer's  Phenomenon.  —  Pfeiffer  found  that  if 
certain  organisms,  such  as  the  cholera  spirillum,  were 
injected  into  the  peritoneal  cavity  of  a  guinea-pig  that 
had  been  immunized  against  these  organisms,  they 
almost  immediately  lost  their  mobility,  and  gradually 
became  granular  and  swollen,  and  subsequently  dis- 
appeared. Later  he  found  that  the  same  phenomenon 
was  present  if  a  small  quantity  of  antiserum  was 
added  to  an  emulsion  of  the  organisms,  and  the  mix- 
ture injected  into  the  peritoneal  cavity  of  a  normal 
guinea-pig.  Later  it  was  shown  by  Metchnikoff  and 
Bordet  that  the  destruction  of  the  bacteria  (bacterio- 
lysis) occurred  outside  the  body  if  to  the  mixture  of 
antiserum  and  bacteria  a  little  fresh  serum  was  added ; 
and  Pfeiffer  found  that  if  the  antiserum  was  heated  at 
from  55°  to  70°  C.  for  an  hour,  and  added  to  the 
bacteria  emulsion,  no  bacteriolysis  would  be  produced, 
but  that  on  the  addition  of  some  fresh  serum  bacterio- 
lysis would  occur. 

Ehrlich  gave  the  name  of  'complement'  to  this 
substance  present  in  fresh  normal  serum  which  had 
the  power  of  enabling  specific  antigens  and  antibodies 
to  produce  their  action. 

46 


NATURE  OF  WASSERMANN  REACTION  47 

Antigen-Antibody  Reactions  and  Complement 
Fixation. — Before  commencing  the  serum  diagnosis 
it  may  be  stated  that  by  '  antigen '  is  meant  a  substance 
which,  when  it  is  introduced  into  a  living  body,  stimu- 
lates the  cells  of  that  body  to  produce  a  substance 
which  destroys  or  neutralizes  it,  and  to  which  the 
name  'antibody'  has  been  given.  It  is  probably  by 
this  antigen-antibody  action  that  recovery  takes  place 
in  most  bacterial  diseases,  and  the  antigen  or  virus 
is  ultimately  neutralized  by  its  specific  antibody.  In 
the  case  of  toxin  and  antitoxin  this  reaction  can  take 
place  directly  in  the  body  or  in  vitro,  and  the  reaction 
appears  to  be  a  purely  chemical  one.  With  cells  or 
micro-organisms,  or  the  extract  or  solution  of  cells  or 
micro-organisms,  however,  the  action  is  more  complex. 
The  antigen  and  antibody  do,  indeed,  become  linked 
together,  but  the  presence  of  a  third  substance  is 
necessary  to  activate  or  stimulate  this  union  of  antigen 
and  antibody  before  the  neutralizing  or  destructive 
process  can  be  completed.  Various  names  have  been 
given  to  this  third  activating  body  by  different  workers, 
but  the  author  will  only  refer  to  it  by  its  most  familiar 
name,  *  complement.' 

The  complement  in  activating  the  mixture  of  antigen 
and  antibody  becomes  used  up,  and  is  therefore  not 
available  for  further  use. 

It  need  hardly  be  mentioned  that  '  lysis '  means 
solution,  and  that  therefore  *  bacteriolysis '  signifies 
solution  of  bacteria,  or  *  haemolysis '  solution  of  red 
corpuscles. 

Antigen  and  antibody  are  generally  specific,  so  that 
a  diphtheria  antigen  produces  only  a  diphtheria  anti- 


48  SYPHILIS  AND  PARASYPHILIS 

body,  and  a  haemolytic  antigen — viz.,  red  blood-cells — 
produces  only  an  antibody  to  the  same  or  closely  allied 
variety  of  blood-cells.  The  specificity  is  so  delicate 
that  strains  of  organisms  so  closely  allied  as  to  be 
morphologically  and  culturally  similar  can  be  differen- 
tiated by  a  complement  fixation  test.  In  the  case  of 
bloods,  however,  when  the  species  are  closely  allied, 
this  method  cannot  be  used  for  differential  diagnosis, 
as  an  antibody  obtained  by  injection  of  a  rabbit  with 
ox  corpuscles  will  produce  haemolysis  of  sheep's 
corpuscles. 

Fischer  uses  the  analogy  of  a  lock  and  key  and 
hand,  for  antigen,  antibody,  and  complement  respec- 
tively. Thus,  as  any  hand  can  turn  any  key  in  its 
own  lock,  the  key  can  only  turn  its  own  lock,  and  the 
key  cannot  turn  in  the  lock  without  the  hand,  so  any 
complement  can  complete  the  action  of  any  combined 
antigen  and  antibody,  but  the  specific  antibody  only 
unites  with  its  own  antigen,  and  the  combined  antigen 
and  antibody  cannot  complete  their  interaction  without 
the  aid  of  complement. 

The  antibody  unites  readily  with  the  antigen  even 
at  room  temperature,  so  that  if,  after  standing  for 
half  an  hour,  the  mixture  of  antibody  and  antigen  be 
centrifuged  and  all  the  serum  removed  with  a  pipette, 
it  will  be  found,  on  the  addition  of  complement  and 
incubation  for  a  while  at  37°  C,  that  the  specific 
action  is  produced,  thus  showing  that  the  essential 
factor  in  the  immune  serum  has  become  linked  to  the 
antigen  during  the  period  when  they  were  in  contact. 

Complement,  however,  which  is  a  normal  and  con- 
stant constituent  of  all  fresh  blood  sera,  is  not  specific 


NATURE  OF  IVASSERMANN  REACTION  49 

(although  probably  several  complements  exist),  and 
can  activate  any  antigen  that  has  united  with  its  own 
antibody.  It  is  as  yet  an  unisolated  and  little  under- 
stood substance,  and  is  really  only  the  name  given  to 
a  property,  present  in  all  fresh  sera,  which  enables  an 
antigen  and  antibody  not  only  to  unite — which,  as 
shown  above,  they  can  readily  do  without  comple- 
ment— but,  having  united,  to  produce  their  specific 
action. 

In  the  Wassermann  reaction  fresh  guinea-pig's  serum 
is  generally  used  for  complement,  for  the  reason  that 
guinea-pig's  serum  contains  a  large  amount  of  com- 
plement (usually  about  five  to  ten  times  as  much  as  a 
similar  quantity  of  rabbit's  serum). 

Complement  has  no  power  of  fixing  by  itself  either 
to  the  antigen  or  antibody. 

The  optimum  temperature  of  a  complementary 
action  is  37°  C. ;  it  is,  however,  capable  of  action 
slowly  at  room  temperature  ;  but  its  action  entirely 
ceases  at  0°  C. 

Antibodies  are  very  stable  and  preserve  their  prop- 
erties for  a  very  long  time,  and  are  not  destroyed  or 
greatly  decreased  in  potency  by  a  temperature  of  55° 
to  57°  C. 

Complement  is  not  a  ferment,  and  a  definite  amount 
of  complement  is  necessary  to  produce  the  action  of 
a  definite  amount  of  antigen  and  antibody ;  so  that  if 
twice  the  amount  of  antigen  is  used,  twice  the  amount 
of  complement  will  be  required. 

Everyone  with  much  experience  of  the  Wassermann 
reaction,  however,  has  noticed  that  with  a  large  excess 
of   antibody  haemolysis   of  the   sheep's  corpuscles  is 

4 


So  SYPHILIS  And  parasyphiUs 

produced  with  a  smaller  quantity  of  complement  than 
would  be  necessary  with  a  smaller  amount  of  anti- 
body. And  the  converse  is  also  true — an  excess  of 
complement  will  produce  haemolysis  with  a  smaller 
quantity  of  antibody. 

Browning  and  Mackenzie  have  aptly  described  this 
interaction  when  they  say  :  '  The  amount  of  antibody 
required  is  a  minimum  when  an  excess  of  complement 
is  present,  and  vice  versa.' 

All  complement  fixation  tests  are  quantitative, 
and  for  this  reason  beginners  are  very  likely  to  be 
led  into  error,  for  a  reading  which  at  one  time  would 
be  reported  as  doubtful,  at  another  time  would  be 
reported  as  positive  or  negative. 

Bordet-Gengou  Phenomenon.  —  The  Bordet- 
Gengou  phenomenon,  discovered  in  1 901,  is  founded 
on  the  elementary  axiom  that  2  into  i  won't  go; 
two  antigens,  two  antibodies,  and  one  complement 
being  used — viz.,  sufficient  complement  to  activate 
one  combined  antigen-antibody.  If,  for  example, 
an  emulsion  of  cholera  vibrios  and  inactivated  anti- 
cholera  serum — i.e.,  serum  containing  cholera  antibody 
which  has  been  decomplementized  by  heating  to  55°  C. 
— is  mixed  with  some  fresh  complement  and  incu- 
bated for  one  hour  at  37°  C,  and  sheep's  corpuscles 
and  a  decomplementized  serum  containing  a  haemo- 
lytic  antibody  are  added,  and  the  mixture  incubated 
for  another  hour,  no  haemolysis  will  take  place, 
because  the  entire  quantity  of  complement  will  have 
been  used  up  in  activating  the  cholera  antigen  which 
has  united  with  the  cholera  antibody,  so  that  solution 
of  the  bacteria  is  produced,  and  therefore  no  comple- 


NATURE  OF  WASSERMANN  REACTION  51 

merit  will  be  left  over  to  activate  the  haemolytic  system 
and  produce  a  solution  of  the  corpuscles. 

The  converse  of  this  experiment  is  also  true  ;  for  if 
sheep's  corpuscles  and  haemolytic  antibody  and  com- 
plement be  mixed  together  and  incubated,  solution  of 
the  corpuscles  will  occur ;  but  if  this  mixture  is  then 
added  to  a  mixture  of  an  emulsion  of  cholera  vibrios 
and  cholera  antibody,  no  solution  of  bacteria  will  now 
occur.  By  this  reaction  antibodies  have  been  found 
and  demonstrated  in  typhoid,  diphtheria,  tubercle, 
gonorrhoea,  dysentery,  cerebro-spinal  meningitis,  and 
leprosy  (James  Mcintosh). 

Wassermann  Reaction.  —  The  Wassermann 
reaction,  as  originally  described,  was  merely  a  modi- 
fication of  the  Bordet-Gengou  reaction,  using  for 
antigen  an  aqueous  or  alcoholic  extract  of  the  liver 
of  a  syphilitic  foetus,  which  experience  has  shown  to 
contain  enormous  numbers  of  SpivochcBta  pallida. 

The  test  was  originally  supposed  to  turn  upon 
ascertaining  the  presence  in  the  tested  serum  of  any 
syphilitic  antibody,  the  extract  of  liver  being  used  as 
antigen.  A  haemolytic  system  is  used  for  the  second 
part  of  the  experiment  in  order  to  test  whether  the 
complement  has  been  used  up  in  the  first  part  of  the 
experiment  or  not. 

The  addition  of  the  haemolytic  system  is  not  an 
essential  part  of  the  test,  but  simply  a  biological 
indicator  for  the  presence  of  complement,  in  the  same 
way  as  the  addition  of  litmus  is  a  chemical  indicator 
for  the  presence  of  an  acid  or  alkali  produced  as  the 
result  of  a  chemical  reaction. 

The  specific  antigen   and   antibody,  or  any  other 


52  SYPHILIS  AND  PARASYPHILIS 

antibody  present  in  a  normal  serum,  can  each  sepa- 
rately absorb  a  small  quantity  of  complement,  but  a 
very  much  greater  quantity  of  complement  is  used  up 
in  activating  the  combined  antigen-antibody,  so  that 
the  specific  antigen  destroying  reaction  can  occur. 
Thus,  if  one  volume  of  complement  is  absorbed  by 
two  volumes  of  specific  antigen,  specific  antibody,  or 
normal  serum,  when  acting  on  each  separately,  making 
three  volumes  in  all,  five,  ten,  or  more  volumes  of 
complement  will  be  absorbed  by  the  combined  specific 
antigen  and  antibody. 

Absolute  alcohol  alone  will  absorb  or  destroy  a 
certain  quantity  of  complement. 

When  testing  for  the  presence  of  any  antibody  in 
the  test  serum,  therefore,  we  must  add  an  excess  of 
complement  over  the  amount  that  could  be  absorbed 
by  specific  antigen,  or  normal  serum. 

If  the  patient's  serum  contains  no  antibody,  the 
complement  will  remain  free,  and  therefore  will  be 
able  to  sensitize  the  h?emolytic  system,  with  the  result 
that  haemolysis  occurs. 

Levaditi  considers  the  Wassermann  reaction  not  due 
to  antibody,  but  to  some  other  substance  produced  by 
a  pathological  metabolism  of  cells.  He  demonstrated 
that  antigen  was  not  true  antigen,  as  extracts  from 
normal  liver  produced  the  reaction,  while  Weil  and 
Braun  showed  that  an  extract  made  from  a  congenital 
syphilitic  liver,  from  which  all  lipoids  had  been  ex- 
tracted, could  still  be  used  as  antigen.  They  also 
demonstrated  that  jaundiced  and  lipaemic  sera  gave 
negative  reactions,  thus  showing  that  lipoids  were  not 
the  cause  of  the  reaction. 


NATURE  OF  WASSERMANN  REACTION  53 

Bordet,  with  his  absorption  theory,  suggested  that 
the  active  substance  in  syphilitic  serum  brings  about 
some  change  in  the  antigen,  so  that  the  altered  antigen 
acquires  a  greater  absorptive  power  for  complement. 
Noguchi  and  others  consider  the  reaction  due  to 
interaction  between  albumin  of  the  antibody  and 
lipoids  of  the  antigen,  probably  as  the  result  of  the 
precipitation  of  some  of  the  colloids  of  the  serum. 

Wassermann  thinks  that  the  antigen  is  derived 
directly  from  the  Spiwchcstd  pallida,  but  this  opinion 
seems  to  be  based  on  data  inconclusive  to  most  other 
workers.  If  the  Wassermann  reaction  is  purely  a 
specific  one,  consisting  of  the  union  of  antigen  (derived 
directly  or  indirectly  from  the  spirochaeta)  and  the 
antibody  present  in  the  infected  patient's  serum,  as 
the  result  of  infection  with  the  spirochseta,  we  should 
expect  that  the  reaction  would  only  be  produced  when 
extracts  from  syphilitic  tissues  were  used.  This, 
however,  is  not  the  case,  and  a  mixture  of  syphilitic 
serum  and  an  extract  of  non-syphilitic  organs  fix  the 
complement  very  nearly,  if  not  quite,  as  satisfactorily. 

Whatever  may  be  the  nature  of  the  reaction,  we 
are  faced  with  the  conclusion  that  clinically  the  test 
is,  with  a  few  exceptions,  pathognomic  of  syphilis, 
and  that  this  test  holds  good  if  substances  are  used 
for  antigen  which  have  nothing  whatever  to  do  with 
syphilis.  Plant  thinks  that  the  most  probable  ex- 
planation is  that  the  antigen  obtained  in  syphilitic  or 
normal  tissue  is  identical,  but  that  syphilitic  organs 
usually  contain  this  antigen  in  larger  amount  or  in 
a  more  easily  extractable  form  than  non-syphilitic 
organs.     He  considers  that  it  is  proved  that  a  sub- 


54  SYPHILIS  AND  PARASYPHILIS 

stance  is  found  in  syphilitic  serum  which  reacts  also 
towards  the  products  of  normal  tissues,  and  that  the 
original  conception  of  the  biological  specificity  of  the 
reaction  is  therefore  no  longer  to  be  held  as  correct  in 
its  full  sense. 

Many  observers  consider  the  antigen  to  be  in  the 
nature  of  a  lipoid,  and  Levaditi  and  Yamanouchi 
further  consider  that  the  antibody  found  in  the 
cerebro-spinal  fluid  of  general  paralytics  is  also  a 
lipoid,  and  soluble  in  alcohol.  Pure  lipoids,  however, 
although  they  fix  complement,  show  but  little  differ- 
ence in  the  quantity  of  complement  they  fix  when 
mixed  with  syphilitic  serum  or  normal  serum. 

Sodium  oleate,  cholesterin,  sodium  glycocolate,  etc., 
have  all  been  proved  to  fix  complement,  but  fix  but 
little  more,  if  any,  in  the  presence  of  syphilitic  sera 
than  they  do  in  the  presence  of  normal  sera. 

Browning  and  Mackenzie  have  found  that  a  mixture 
of  cholesterin  and  lecithin  not  only  fixes  much  more 
complement  than  either  of  the  constituents  of  the 
mixture  by  itself,  but  that  much  more  complement 
is  fixed  in  the  presence  of  syphilitic  sera  than  in  the 
presence  of  normal  sera.  The  author  has  investigated 
their  claim  in  over  a  hundred  sera,  having  made 
parallel  tests  of  the  same  sera,  using  extract  of 
syphilitic  organs,  extract  of  normal  organs,  and 
cholesterin  -  lecithin  mixture  as  antigen,  and  has 
obtained  practically  identical  results  with  all  three. 

As  regards  the  serum,  exposure  to  a  temperature 
of  55°  to  57°  C.  for  half  an  hour  certainly  seems  to 
diminish  the  reaction.  Prolonged  exposure  at  these 
temperatures  can  destroy  the  reacting  power  altogether. 


NATURE  OF  WASSERMANN  REACTION  55 

Bruck  considers  that  a  temperature  of  60°  C.  increases 
the  complement  fixing-power  of  sera  by  themselves. 
It  has  also  been  shown  that  normal  sera  may  have  a 
complement  fixing-power  in  the  unheated  state  which 
disappears  if  it  is  heated  at  55**  C. 

No  definite  conclusion  has  yet  been  arrived  at  as  to 
what  the  Wassermann  reaction  really  is. 

Weil  and  Braun  consider  that  in  the  course  of  the 
disease  tissue-products,  mixtures  of  albumin  and  lipoid 
probably,  are  absorbed  and  give  rise  to  antibodies. 

Citron  considers  that  the  syphilitic  toxin  becomes 
combined  with  lipoids,  and  that  this  combination  of 
toxin  and  lipoid  acts  as  an  antigen,  and  leads  to  the 
production  of  an  antibody  in  the  sera. 

Bruck  and  Stern  think  that  the  reaction  may  be 
brought  about  by  the  interaction  between  mixtures 
of  albumin  and  lipoid  found  in  the  extract  and 
mixtures  of  albumin  and  lipoid  found  in  the  serum. 

Mott  considers  that  the  substance  present  in  the 
serum  or  cerebro-spinal  fluid  necessary  to  produce  the 
reaction  may  be  the  detachable  products  of  nerve- 
tissues. 

Neither  lecithin  nor  cholesterin,  if  used  as  antigen, 
can  produce  antibody. 

Plant  comes  to  the  conclusion  : 

I.  That  the  Wassermann  reaction  is  a  biological 
specific  antigen-antibody  reaction  for  syphilis,  in  which 
the  antibodies  on  the  one  side  have  the  peculiarity  of 
reacting,  not  alone  with  syphilitic  antigen,  but  also 
with  normal  tissue  constituents,  and  that  the  antigen, 
on  the  other  hand,  is  very  closely  related  to  the  lipoids, 
and  probably  is  an  albumin  lipoid  compound. 


56  SYPHILIS  AND  PARASYPHILIS 

2.  The  reacting  substances  of  the  syphilitic  serum 
are  not  antibodies,  but  substances  which  owe  their 
origin  to  syphiUtic  infection  and  possess  a  chemical 
affinity  for  lecithin. 

3.  In  the  Wassermann  reaction  specific  and  non- 
specific fixation  processes  go  hand  in  hand. 

That  the  complement-fixing  substance  (antibody) 
exercises  no  spirochaeticidal  action  has  been  proved  by 
experiments  both  in  vivo  and  in  vitro.  In  the  one  case 
an  ape  was  injected  with  large  quantities  of  serum 
containing  a  large  amount  of  complement  -  fixing 
substance  which,  however,  did  not  prevent  successful 
inoculation  with  syphilitic  virus,  and  in  the  second 
serum  obtained  from  a  chancre,  and  containing  large 
numbers  of  spirochaetes,  was  treated  with  a  mixture  of 
complement  and  serum  containing  a  large  amount  of 
complement-fixing  substance.  This  mixture  was  then 
used  to  inoculate  an  ape,  with  positive  results. 

According  to  Citron's  theory,  mentioned  above,  the 
antibody  produced  is  one  in  which  the  mixture  of 
toxin  and  lipoid  is  the  antigen  and  not  the  spirochaete. 
This  antibody,  therefore,  could  not  be  expected  to 
produce  immunity  to  the  Spirochceta  pallida^  which 
agrees  with  experimental  findings. 

Weil  and  Braun  found  that  an  extract  of  syphilitic 
liver  from  which  all  lipoids  were  removed  yet  remained 
an  efficient  antigen. 

Mcintosh  and  Fildes  point  out  that  Sach's  observa- 
tion that  the  Wassermann  bodies  are  destroyed  by  a 
temperature  which  does  not  affect  true  antibodies,  and 
that  Satta  and  Donetti's  demonstration  that  fixation 
of  complement  in  the  Wassermann  reaction  can  take 


NATURE  OF  WASSERMANN  REACTION  57 

place  in  the  ice-chest  as  well  as  at  37°  C,  and  Muter- 
milch  and  Mcintosh's  observations  that  the  Wasser- 
mann  body  does  not  pass  through  a  filter,  all  tend  to 
show  that  the  reaction  is  rather  physico-chemical  than 
biological. 

The  effect  of  treatment,  also,  is  to  destroy  the 
Wassermann  body,  and  not  to  produce  it,  the  dis- 
appearance of  symptoms  coinciding  with  the  dimi- 
nution or  loss  of  complement  -  fixing  substance. 
This  is  paricularly  striking  after  treatment  with 
salvarsan. 

The  physico-chemical  theory  was  first  suggested  by 
Levaditi  and  Yamanouchi,  who  thought  that  the  fixa- 
tion of  complement  was  due  to  an  interaction  between 
substances  in  the  serum  and  in  the  extract  used  as 
antigen,  so  that  the  resulting  mixture  had  a  greater 
affinity  for  complement. 

Wolfsohn  and  Reicher,  and  later  Boas  and  Petersen, 
have  shown  that  if  blood  is  obtained  towards  the  end 
of  a  period  of  deep  anaesthesia,  some  specimens  will 
give  a  positive  Wassermann  reaction.  These  experi- 
ments certainly  suggest  that  the  reaction  is  produced 
by  some  form  of  cell  destruction,  and  could  not  be  the 
result  of  an  antibody. 

The  high  percentage  of  positive  Wassermanns 
obtained  with  blood  taken  from  the  cadaver  also 
supports  this  view. 

From  the  above  opposing  theories,  and  from  the 
rather  contradictory  nature  of  the  evidence  at  present 
available,  it  is  obvious  that  the  precise  nature  of  the 
reaction  has  yet  to  be  discovered.  We  are,  however, 
able  to  arrive  at  two  conclusions  : 


58  SYPHILIS  AND  PARASYPHILIS 

1.  That  the  reaction  in  the  absence  of  a  few 
diseases  and  conditions,  which  can  easily  be  eliminated, 
is  a  reliable  clinical  test  for  syphilitic  infection. 

2.  That  the  reaction  is  not  strictly  specific,  that  the 
substance  produced  is  not  a  true  antibody,  and  that 
the  so-called  antigen  is  not  a  true  antigen. 


CHAPTER  V 

PREPARATION  AND  TITRATION  OF  RE- 
AGENTS REQUIRED  FOR  WASSER- 
MANN  REACTION 

The  materials  required  in  the  original  method  for  the 
estimation  of  the  Wassermann  reaction  are  five  in 
number. 

1.  Syphilitic  antigen,  or  rather  pseudo-antigen, 
prepared  either  from  syphilitic  organs,  normal  organs, 
or  lecithin  and  cholesterin. 

2.  The  patient's  blood-serum. 

3.  Complement  from  fresh  guinea-pig's  serum. 

4.  Washed  sheep's  corpuscles  (haemolytic  antigen). 

5.  A  serum  haemolytic  to  sheep's  corpuscles 
(haemolytic  antibody). 

I.  Syphilitic  Pseudo- Antigen. 

(i)  Extract  of  Syphilitic  Organs  as  prepared 
by  Noguchi  and  Mott. — The  weighed  liver  of  a 
syphilitic  foetus  is  ground  up  with  a  sufficient  quantity 
of  silver-sand  and  plaster  of  Paris,  so  that  after  a  few 
hours  it  can  be  reduced  to  a  powder  ;  this  powder  is 
then  washed  with  acetone,  which  removes  bodies 
which     have     anticomplementary     and     haemolytic 

59 


6o  SYPHILIS  AND  PARASYPHILIS 

properties.  The  acetone  is  then  filtered  off,  and 
the  remaining  solid  material  is  allowed  to  dry  at 
room  temperature.  The  dry  residue  is  then  trans- 
ferred to  a  flask  and  a  sufficient  quantity  of  alcohol 
added  ;  this  flask  is  kept  at  room  temperature  and 
occasionally  shaken.  After  two  days  the  alcoholic 
extract  is  filtered  off,  and  the  filtrate  made  up  with 
alcoholic  washings  of  the  powdered  organ  so  that 
4  c.c.  is  equivalent  to  i  gramme  of  liver.  The  extract 
keeps  well  for  several  months  without  much  deteriora- 
tion, and  should  be  stored  in  the  dark  and  in  the  cold. 

(2)  Extract  of  Normal  Organs. — Human  heart, 
ox's  heart,  guinea-pig's  heart,  all  have  their  advocates, 
but  personally  the  author  prefers  an  extract  of  rabbit's 
heart,  with  which  excellent  results  have  been  obtained. 
The  heart  should  be  fresh,  should  be  washed  in  saline 
to  remove  all  blood,  as  much  connective  tissue  as 
possible  should  be  removed,  and  the  opened  heart 
roughly  dried  between  filter-paper.  The  heart  is  now 
weighed  and  afterwards  cut  up  into  small  pieces  with 
scissors.  A  little  absolute  alcohol  is  added,  and  the 
mixture  well  ground  in  a  pestle  and  mortar.  More 
alcohol  is  slowly  added,  till  the  final  quantity  of  10  c.c. 
of  alcohol  to  I  gramme  of  heart  is  reached.  The  mix- 
ture is  kept  in  a  stoppered  bottle  at  room  temperature 
for  two  days,  and  occasionally  shaken ;  it  is  then  centri- 
fuged,  and  the  supernatant  fluid  pipetted  off  and  stored 
in  the  cold  and  in  the  dark. 

(3)  Mixture  of  Lecithin  and  Cholesterin 
(Browning,  Cruikshank,  and  Mackenzie). — The  lecithin 
is  obtained  by  making  an  alcoholic  extract  of  fresh  and 
finely  minced  ox  liver,  one  part  of  liver  being  taken  to 


PREPARATION  OF  REAGENTS  6i 

four  parts  of  95  per  cent,  alcohol.  This  is  kept  at  room 
temperature  and  occasionally  stirred  ;  after  four  days 
the  supernatant  fluid  is  pipetted  off  and  evaporated  at 
60°  C.  till  a  syrupy  mass  remains.  This  is  treated  in 
succession  with  ethyl-acetate,  water-free  ether,  and 
acetone,  and  the  alcoholic  lecithin  solution  so 
obtained  is  kept  in  a  stoppered  bottle  in  the  dark. 
The  cholestevin  used  by  the  authors  of  this  method 
was  obtained  from  Kahlbaum  or  Roulene  Fr^res. 
It  is  added  in  excess  to  a  075  solution  of  lecithin 
in  alcohol.  As  saturation  occurs  only  slowly  at 
room  temperature,  the  mixture  should  be  allowed  to 
stand  for  a  week  before  the  clear  fluid  is  drawn  off  and 
stored  for  use.* 

A  good  antigen,  no  matter  how  prepared,  is  one 
producing  a  large  deflection  of  complement  in  the 
presence  of  a  syphilitic  serum,  and  which  fixes  but 
little  complement  by  itself  or  in  the  presence  of  a 
normal  serum.  Absolute  alcohol  alone  and  alcoholic 
extracts  in  the  presence  of  normal  sera  have  power 
to  fix  a  certain  amount  of  complement. 

When  standardizing  the  antigen  various  quantities 
of  antigen  are  added  to  test-tubes  containing  constant 
quantities  of  syphilitic  serum  and  complement,  and 
the  tube  noted  in  which  the  smallest  amount  of 
antigen  is  capable  of  producing  complete  inhibition 
of  haemolysis,  indicating  complete  fixation  of  comple- 
ment. 

*  Particulars  of  the  method  of  preparation  will  be  found  in 
Browning  and  Mackenzie's  book  on  '  Recent  Methods  of 
Diagnosis  and  Treatment  of  Syphilis,'  p.  38.  The  mixed 
alcoholic  solution  of  lecithin  and  cholesterin  can  be  obtained 
from  Messrs.  Thompson,  Skinner,  and  Hamilton,  38,  Sauchiehall 
Street,  Glasgow. 


62  SYPHILIS  AND  PARASYPHILIS 

A  second  row  of  test-tubes  contain  complement  and 
antigen  alone,  and  no  serum  ;  and  a  third  row  com- 
plement and  antigen,  and  normal  serum  in  place  of 
the  syphilitic  serum.  The  antigen  selected  for  use 
should  fix  very  little  complement  by  itself  alone  pr 
in  the  presence  of  normal  serum,  and  at  least  three 
times  as  much  antigen  should  be  necessary  to  fix  a 
given  quantity  of  complement  with  normal  serum 
than  would  be  required  with  syphilitic  serum. 

2.  Patient's  Serum. 

Test  Serum. — The  blood  is  collected  in  a  sterile 
tube.  After  being  allowed  to  stand  for  a  couple 
of  hours,  it  is  centrifuged  and  the  clear  serum  drawn 
off  with  a  sterile  pipette,  sealed  in  small  sterile  glass 
phials,  heated  in  a  water-bath  at  a  temperature  of 
5^°  C.  for  fifteen  minutes  in  order  to  destroy  the 
complement  which  it  contains,  and  stored  in  a  cool 
place  in  the  dark.  It  is  preferable  to  have  a  con- 
siderable quantity  of  serum,  so  that  a  quantitative 
measurement  of  the  complement-fixing  substance  may 
be  undertaken,  and  in  order  that  the  experiments  may 
be  repeated  should  the  controls  not  work  out  satis- 
factorily. For  this  reason  the  author  prefers  obtaining 
blood  by  venipuncture  rather  than  by  pricking  the 
finger.  When  collecting  numerous  samples  of  blood 
by  venipuncture,  the  use  of  a  syringe  necessitates 
a  considerable  waste  of  time,  as  the  syringe  cannot, 
after  use,  be  plunged  into  boiling  water  for  re- 
sterilization  without  great  danger  of  cracking,  neither 
can  it  safely  be  removed  from  boiling  water.  If  the 
temperature  is  gradually  raised  to  boiling-point,  and 


PREPARATION  OF  REAGENTS  63 

then  lowered,  at  least  ten  minutes  will  be  required  for 
each  case.  Instead  of  a  syringe,  therefore,  the  author 
uses  a  hollow  metal  holder,  2|  inches  long,  having 
a  finger-grip  half  an  inch  from  the  nozzle  end.  The 
bulbous  distal  end  is  connected  to  about  4  inches  of 
rubber  tubing,  leading  to  a  sterile  test-tube,  into 
which  the  blood  flows  directly  (see  Fig.  14).  The 
author  uses  needles  i  inch  long,  and  with  the  calibre 
of  a  large  exploring  needle. 

Technique. — After  washing  the  bend  of  the  elbow 
with  ether  and  absolute  alcohol,  a  firm  bandage  is 
applied  round  the  upper  arm,  and  the  patient  is  told 


Fig.  14. — Venipuncture  Needle  and  Holder  (Author's 

Pattern). 

*  to  make  a  fist.'  Either  the  median  basilic  or  median 
cephalic  vein  can  then  easily  be  seen.  The  needle, 
after  being  lubricated  with  sterile  oil,  is  plunged  boldly 
into  the  vein  with  a  quick  stab,  keeping  the  needle  and 
holder  in  the  direction  of  the  long  axis  of  the  vein, 
taking  care  not  to  depress  the  point  too  much  in  order 
to  avoid  transfixing  the  vein.  The  blood  will  flow 
directly  into  the  tube,  and  it  will  only  take  a  few 
seconds  to  half  fill  it.  The  glass  test-tube  and  the 
needle-holder,  with  the  rubber  tubing  leading  into  the 
test-tube,  can  be  held  quite  easily  in  the  right  hand. 
Before  making  the  puncture,  the  skin  over  the  vein 
should  be  rendered  tense  and  pulled  a  little  down  over 


64  SYPHILIS  AND  PARASYPHILIS 

with  the  thumb  of  the  left  hand.  The  bandage  must 
be  loosened  and  the  patient  told  to  unclasp  his  hand 
before  the  needle  is  removed,  otherwise  a  subcutaneous 
haematoma  may  be  produced.  If  a  small  pad  is  held 
over  the  puncture,  and  the  patient  told  to  hold  his 
arm  in  the  air  for  a  few  minutes,  there  will  be  no 
bleeding,  and  no  dressing  will  be  required.  The 
author  always  places  a  sterile  swab  soaked  with 
methylated  spirit  over  the  puncture  before  removing 
the  needle,  and  in  this  way  not  a  single  drop  of  blood 
escapes,  except  into  the  test-tube,  and  the  patient 
sees  no  blood  at  all. 

After  standing  for  a  few  hours  to  permit  the  serum 
to  separate  from  the  clot,  the  serum  is  withdrawn  with 
a  pipette  made  by  drawing  out  glass  tubing  (Fig.  15). 
It  is  then  placed  in  small  sterile  phials,  which  are 
sealed  in  the  flame,  and  the  sealed  phials  are  immersed 
in  a  water-bath  at  a  temperature  of  ^^°  C.  for  fifteen 
minutes  to  destroy  the  complement  contained  in  the 
serum. 

After  use,  the  holder  and  rubber  tube  should  be 
washed  through  with  a  small  glass  urethral  syringe  to 
remove  the  blood  before  replacing  in  the  sterilizer. 

If,  as  very  occasionally  happens,  a  patient  objects 
to  venipuncture,  or  a  vein  of  sufficient  size  cannot  be 
found,  or,  as  with  children  or  infants,  the  test  has  to  be 
undertaken  with  a  smaller  quantity  of  serum,  then  in 
these  cases  the  blood  is  obtained  by  pricking  the  finger, 
or,  as  the  author  usually  finds  more  suitable  with  small 
infants,  the  great  toe  or  heel.  In  small,  marasmic 
infants  it  will  be  necessary  to  soak  the  limb  in  hot 
water   before    pricking.      The    blood   is   collected   in 


PREPARATION  OF  REAGENTS  65 

large    Widal    tubes,    which    are    filled    by    capillary 
attraction. 

3.  Complement, 

This  is  obtained  from  fresh  guinea-pig's  serum, 
a  guinea-pig  being  selected  because  its  blood  is  very 
rich  in  complement,  and  its  complement  content  is 
very  nearly  constant ;  guinea-pig's  serum  usually 
contains  from  five  to  ten  times  the  amount  of 
complement  found  in  rabbit's,  horse's,  or  human 
blood.  The  author  thinks  that  the  largest  amount 
of  serum  is  obtained  from  a  guinea-pig  in  the  fol- 
lowing way :  Some  cotton-wool  is  placed  in  the 
bottom  of  a  wide-necked  glass  jar  of  such  a  size  as  to 
easily  admit  the  guinea-pig's  head  ;  a  few  drachms  of 


Fig.  15. — Pipette  for  drawing  off  Blood  or  Serum. 
(One-third  natural  size.) 

ether  are  poured  on  the  cotton-wool,  and  the  jar  is 
then  slipped  over  the  guinea-pig's  head.  When  anaes- 
thesia is  complete,  the  chest  is  opened  and  the  blood 
removed  by  puncturing  the  heart  with  a  pipette 
(Fig.  15).  If  the  heart  and  lungs  are  now  removed, 
a  little  additional  blood  can  be  collected  from  the 
thoracic  cavity.  After  standing  for  a  quarter  of  an 
hour,  the  blood  should  be  whipped  for  a  few  minutes 
and  then  centrifuged,  when  the  clear  serum  is  pipetted 
off.  The  author  thinks  it  is  best  to  prepare  the  com- 
plement on  the  evening  before,  and  store  it  in  the 
ice-chest  for  use  the  following  day. 

5 


66  SYPHILIS  AND  PARASYPHILIS 

The  complement-content  of  fresh  guinea-pig's  serum 
does  not  usually  vary  very  much,  but  it  is  wise  to  put 
up  three  tubes  containing  the  amount  of  complement 
to  be  used  in  the  test,  and  containing  respectively  the 
usual  quantities  of  antigen  alone,  antigen  and  normal 
serum,  and  antigen  and  syphilitic  serum.  Complete 
haemolysis  should  be  produced  in  all  but  the  tube  con- 
taining the  syphilitic  serum,  in  which  there  should  be 
no  haemolysis. 

4  and  5.  Haemolytic  System. 

(a)  Sheep's  Corpuscles.  —  Fresh  blood  is  col- 
lected at  the  slaughter-house  into  a  sterilized  wide- 
necked  glass  bottle  containing  several  pieces  of  wire. 
The  bottle  is  half  filled  with  blood,  when  it  is 
securely  stoppered  and  briskly  shaken  for  ten  minutes. 
The  fibrin  will  be  deposited  on  the  wires,  and  10  c.c. 
of  the  defibrinated  blood  is  centrifuged  and  the 
supernatant  fluid  pipetted  off.  Normal  saline  solu- 
tion is  added  to  the  deposit  of  red  cells,  which  are 
shaken  up,  and  the  mixture  of  salt  solution  and 
corpuscles  again  centrifuged.  The  supernatant  fluid  is 
again  pipetted  off  and  thrown  away,  and  fresh  normal 
saline  added  to  bring  the  volume  up  to  the  original 
10  c.c.  In  this  way  a  suspension  of  sheep's  corpuscles 
free  from  serum  and  complement  is  obtained. 

Eight  c.c.  of  this  suspension  is  added  to  92  c.c.  of 
normal  saline  solution,  producing  an  8  per  cent,  solution 
of  washed  sheep's  corpuscles,  which  is  the  strength 
the  author  employs.  If  stored  in  an  ice-chest,  the 
corpuscles  will  usually  keep  three  or  four  days  without 
haemolyzing. 


PREPARATION  OF  REAGENTS  67 

Some  observers  consider  that  greater  accuracy  is 
demanded,  and  count  the  corpuscular  suspension  with 
the  Throma-Zeiz,  in  this  way  insuring  that  the  cor- 
puscular suspension  is  always  constant  as  regards 
numbers.  It  appears  to  the  author,  however,  that 
different  corpuscular  suspensions  vary  in  their  sus- 
ceptibility to  haemolysis,  and  that  therefore  we  cannot 
insure  that  any  two  corpuscular  suspensions  are 
constant  factors. 

The  quantity  of  immune  body  required  is  in  direct 
proportion  to  the  number  of  red  cells,  a  20  per  cent, 
suspension  requiring  just  twice  as  much  haemolytic 
serum  to  produce  complete  haemolysis  as  does  a 
10  per  cent,  suspension. 

Some  authorities  consider  that  the  corpuscles  keep 
longer  if  a  little  formalin  has  been  added  to  the  normal 
saline  solution  (in  proportion  of  o*i  per  cent.).  Per- 
sonally, the  author  prefers  to  use  fresh  blood,  as  he 
thinks  that  the  formalin  tends  to  harden  the  corpuscles 
and  retard  or  prevent  haemolysis. 

(b)  Haemolytic  Serum. — This  can  be  obtained  by 
treating  a  rabbit  with  washed  sheep's  corpuscles. 
The  rabbit  may  be  injected  either  intravenously  in 
the  marginal  auricular  vein  or  intraperitoneally.  In 
the  latter  case,  which  is  easier,  but  perhaps  not  quite 
so  satisfactory,  the  rabbit  should  be  held  with  its  head 
downwards,  the  abdominal  walls  being  grasped  with 
the  fingers  and  thumb  of  the  left  hand  so  as  to  make 
a  fold  containing  no  intestines,  and  this  is  transfixed 
with  a  needle  attached  to  the  syringe  containing  the 
sheep's  corpuscles.  When  the  left  hand  is  taken 
away,  the  fold  disappears  and  the  needle  is  withdrawn, 


68  SYPHILIS  AND  PARASYPHILIS 

SO  that  the  point  re-enters  the  abdominal  cavity;  the  con- 
tents of  the  syringe  are  now  injected  into  the  peritoneal 
cavity,  and  the  needle  removed.  Usually  about  three 
injections  are  required  to  obtain  a  potent  serum,  the 
injections  being  given  at  intervals  of  four  to  six  days. 

Recently,  Burroughs  and  Wellcome  have  placed  a 
haemolytic  serum,  obtained  from  the  horse,  on  the 
market,  and  the  author  has  found  it  quite  satisfactory 
in  use.  The  horse  serum,  however,  contains  hsemo- 
agglutinins  as  well  as  haemolysins,  but  the  agglutinins 
do  not  act  in  dilution  above  i  in  400.  It  is  important, 
therefore,  that  the  serum  should  have  a  high  haemolytic 
titre,  such  as  i  in  800  or  i  in  1,000,  as,  if  agglutination 
occurs,  the  red  cells  clump  and  fall  to  the  bottom  of 
the  test-tube  before  the  hsemolysin  has  had  time  to 
act  on  them  and  dissolve  them. 

Haemolytic  serum,  whether  obtained  from  the  rabbit 
or  the  horse,  keeps  its  haemolytic  power  for  a  long 
time,  and  the  haemolytic  titre  falls  very  gradually  as 
a  rule. 

The  haemolytic  serum  should  be  used  in  excess, 
about  twice  the  haemolytic  dose  being  recommended 
by  Wassermann.  Varying  dilutions  of  haemolytic  serum 
are  added  to  tubes  containing  constant  quantities  of 
complement  and  suspension  of  sheep's  corpuscles,  and 
the  tube  noted  in  which  complete  haemolysis  is  just 
produced  in  five  minutes  in  a  water-bath  at  a  tem- 
perature of  37°  C. 

If  a  smaller  dilution  than  i  in  400  is  necessary,  the 
serum  cannot  be  considered  satisfactory,  as  agglutina- 
tion of  the  corpuscles  may  be  produced,  which  may 
interfere  with  the  action  of  the  haemolysin. 


PREPARATION  OF  REAGENTS  69 

A  rapid  dilution  can  be  effected  in  the  following 
way:  Into  two  test-tubes  measure  9  c.c.  of  saline 
solution  ;  to  the  first  add  i  c.c.  of  the  haemolytic  serum 
to  be  tested,  shake  and  add  i  c.c,  of  this  to  the  second ; 
this  will  give  a  solution  of  i  in  100.  Now  put  5  c.c. 
of  saline  into  five  test-tubes  and  to  the  first  tube  add 
5  c.c.  of  the  mixture  from  the  test-tube  containing  the 
dilution  of  i  in  100,  shake  and  take  5  c.c.  of  this  and 
add  it  to  the  next  tube,  and  so  on.  In  this  way  dilu- 
tions of  I  in  200,  400,  800,  1,600,  and  3,200  will  be 
rapidly  effected.  If  complete  haemolysis  is  produced 
in  I  c.c.  of  an  8  per  cent,  suspension  of  sheep's 
corpuscles  containing  0-05  c.c.  of  fresh  guinea-pig's 
serum  with  i  c.c.  of  haemolytic  serum  in  a  dilution 
of  I  in  800  to  1,600,  the  haemolytic  serum  may  be 
considered  a  good  one. 


CHAPTER  VI 

WASSERMANN  REACTION 

ORIGINAL  TECHNIQUE 

Quantitative  Measurement  by  Variation  in 
Amount  of  Complement. 

The  first  technique  described  is  a  modification  of 
Neisser's  and  Wassermann's  that  the  author  uses, 
and  in  which  all  the  essentials  of  Wassermann's 
original  technique  are  preserved. 

Two  test-tubes  are  required  for  each  serum  ex- 
amined, whether  sera  to  be  tested  or  controls.  The 
latter  consist  of  a  known  syphilitic  serum,  a  known 
normal  serum,  and  a  tube  without  any  serum  at  all. 

The  tubes  are  arranged  in  two  rows,  those  in  the 
back  row  containing  three  times  as  much  complement 
as  the  front  row,  so  as  to  obtain  a  roughly  quantitative 
estimation  of  the  complement  fixing-povver  of  the 
serum.  The  quantities  of  the  various  ingredients, 
which  the  author  has  found  to  be  most  convenient, 
are — For  the  front  row,  i  c.c.  of  normal  salt  solution, 
o"i  c.c.  of  antigen,  and  o"05  c.c.  of  fresh  guinea-pig's 
serum  per  each  tube.  Considerable  time  is  saved 
and  greater  accuracy  obtained  if  these  three  constant 
factors  (salt  solution,  antigen,  and  complement  serum) 

70 


WASSERMANN  REACTION  -ji 

are  first  mixed  in  bulk  (instead  of  separately  in  each 
test-tube)  and  afterwards  i  c.c.  of  the  mixture  measured 
into  the  test-tubes,  to  which  0*15  c.c.  of  the  serum  to 
be  tested  is  added.  Let  us  suppose  that  there  are 
seven  sera  to  be  examined,  making  a  total  of  ten  with 
the  three  controls.  Ten  c.c.  of  saline  solution  are 
then  taken,  i  c.c.  of  antigen,  0*5  c.c.  of  fresh  guinea- 
pig's  serum.  These  are  well  mixed  together,  and 
I  c.c.  of  the  mixture  put  into  each  of  the  test-tubes  in 
the  front  row.  For  the  back  row  similar  quantities 
of  saline  and  antigen  are  used,  but  three  times  the 
amount  of  complement — namely,  o'i5  c.c.  per  each 
tube,  or  1*5  c.c.  for  the  ten.  By  this  mixing  of  the 
saline,  extract,  and  complement  in  bulk,  only  two 
pipette  measurements  are  required  instead  of  four, 
which  would  be  necessary  if  the  saline,  antigen,  com- 
plement, and  test-serum  were  added  separately  to  each 
tube. 

If  the  antigen  alcoholic  extract  is  mixed  with  the 
full  quantity  of  normal  saline,  only  a  slight  opalescence 
is  produced.  If,  however,  the  antigen  extract  is  first 
mixed  with  its  own  quantity  of  saline,  a  marked 
turbidity  results,  and  if  this  is  then  added  to  the  rest 
of  the  saline,  the  turbidity  remains.  Browning  and 
Mackenzie  and  the  author,  working  independently, 
arrived  at  the  conclusion  that  the  best  results  were 
obtained  when  the  turbid  emulsion  was  used,  and  this 
is  still  the  author's  opinion.  Macintosh  and  Fildes, 
on  the  other  hand,  consider  that  if  a  turbid  emulsion 
is  used,  there  is  a  liability  to  complement  fixation  even 
with  normal  sera,  and  they  recommend,  therefore,  that 
the  antigen  extract  should  be  rapidly  mixed  with  the 


72  SYPHILIS  AND  PARASYPHILIS 

full  quantity  of  serum,  so  that  there  may  be  as  little 
turbidity  as  possible. 

The  neck  of  the  ampule  containing  the  decomple- 
mentized  test-serum  is  now  broken  off  and  the  required 
quantity  (0-15  c.c.)  removed  with  a  teat-pipette 
(Fig.  16)  and  added  to  the  front  row  and  corre- 
sponding back-row  tubes. 

After  adding  the  0*15  c.c.  of  the  various  sera  to  be 
tested  to  their  respective  tubes,  using  the  same 
quantity  for  both  front  and  back  rows,  the  tubes  are 
inverted,  keeping  the  thumb  over  the  open  end,  so  as 
to  diffuse  the  serum  equally  in  the  test-tubes.  The 
test-tube  rack  is  now  placed  in  a  water-bath  at  37°  C. 


Fig.  16. — Teat-Pipette,  marked  to  measure  o"i5  c.c. 

for  half  an  hour  (Fig.  17).  Having  previously 
ascertained  the  strength  of  the  haemolytic  serum,  a 
dilution  of  such  serum  is  now  prepared  of  such  a 
strength  that  each  tube  will  contain  twice  the  dose 
necessary  to  produce  complete  haemolysis  in  i  c.c.  of 
an  8  per  cent,  suspension  of  washed  sheep's  corpuscles. 
Let  us  suppose  that  the  haemolytic  serum  previously 
tested  produced  complete  haemolysis  of  an  8  per  cent, 
suspension  of  sheep's  corpuscles  in  a  dilution  of  i  in 
1,600.  We  must  obtain  a  dilution  of  i  in  800  in  the 
final  test.  For  our  twenty  tubes  (ten  in  each  row)  we 
required  20  c.c.  of  the  sensitized  corpuscles ;  we 
therefore  take  10  c.c.  of  a  dilution  of  i  in  200  of 
haemolytic  serum  and  add  to  it  10  c.c.  of  an  8  per  cent, 
suspension  of  sheep's  corpuscles,  when  we  shall  have 


WASSERMANN  REACTION  73 

a  dilution  of  i  in  400,  making  20  c.c.  in  all ;  this 
mixture  of  htemolytic  antigen  and  antibody  is  called 
the  '  haemolytic  system.'  One  c.c.  of  this  mixture  is 
then  added  to  each  of  the  tubes  which  have  been 
incubated  for  half  an  hour,  so  that  the  final  dilution 
of  I  in  Soo  is  arrived  at.     The  tubes  are  now  inverted 


Fig.   17. — "Water-Bath. 

again  and  replaced  in  the  water-bath  until  such  time 
as  complete  solution  of  the  corpuscles  is  produced  in 
the  two  control-tubes  containing  normal  serum  and  no 
serum.  When  complete  solution  occurs  in  these  two 
control-tubes,  the  test-tube  rack  can  be  removed  from 
the  water-bath  and  the  tubes  examined. 


74  SYPHILIS  AND  PARASYPHILIS 

If  the  test-tube  contains  serum  from  a  case  of 
syphilitic  infection,  a  substance  having  the  power  of 
uniting  with  the  antigen  will  be  present,  and  the 
complement  will  have  been  used  up  by  these  two 
combined  substances.  There  will  therefore  be  no 
complement  left  over  for  the  second  incubation  period 
after  the  haemolytic  antibody  and  antigen,  were  added. 
No  haemolysis  can  take  place  in  these  tubes,  and  the 
suspension  of  corpuscles  will  remain  opaque.  On 
standing,  the  corpuscles  will,  after  a  few  hours,  sink 
to  the  bottom  of  the  test-tube,  and  the  supernatant 
fluid  will  be  clear  and  colourless  if  the  inhibition  of 
haemolysis  has  been  complete.  If,  on  the  other  hand, 
the  test-serumx  is  free  from  syphilitic  infection,  the 
substance  having  the  power  to  unite  with  the  antigen 
will  be  absent ;  the  complement  will,  therefore,  not  be 
used  up,  and  will  be  free  to  activate  the  haemolytic 
system,  and  solution  of  the  corpuscles  will  occur  and 
a  clear  red  solution  be  obtained. 

Between  the  two  extremes  of  complete  inhibition  of 
haemolysis  and  complete  haemolysis  there  may  be 
many  degrees  of  partial  haemolysis  which  must  be 
estimated  by  the  amount  of  undissolved  red  cells  at 
the  bottom  of  the  test-tubes  and  the  depth  of  tint  of 
the  supernatant  fluid. 

The  haemolytic  system  should  be  prepared  and 
incubated  at  37°  C.  for  a  short  while  before  being 
used,  so  that  the  corpuscles  may  be  fully  sensitized 
and  only  require  the  addition  of  complement  to 
produce  rapid  haemolysis. 

It  will  be  found  that  a  strongly  positive  serum  will 
contain  sufficient  complement-fixing  substance  to  fix 


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WASSERMANN  REACTION  75 

the  triple  dose  of  complement  in  the  back  row,  but  that 
in  some  cases  only  sufficient  will  be  present  to  fix  the 
smaller  dose  of  complement  in  the  front  row,  and 
complete  haemolysis  may  be  produced  in  the  back  row 
(Fig.  18). 

Frequently,  as  a  patient  comes  under  the  influence 
of  treatment,  the  blood  will  pass  through  the  stages 
of— 

(i)  Complete   inhibition   of   haemolysis   in   front 
and  back  tubes  ; 

(2)  Complete   inhibition    of    haemolysis   in    front 

tubes,    partial     haemolysis     in    the    back 
tubes ; 

(3)  Complete  inhibition  in  the  front  tubes,  com- 

plete haemolysis  in  the  back  tubes  ; 

(4)  Partial  haemolysis  in  the  front  tubes  ; 

until  finally  a  completely  negative  reaction  is  reached 
— namely : 

(5)  Complete  haemolysis  in  front  as  well  as  back 

tubes. 

The  author  uses  the  symbol  +  to  denote  complete 
inhibition  of  haemolysis,  ±  to  denote  partial  haemolysis, 
and  -  to  denote  complete  haemolysis. 

If  the  left-hand  symbol  of  each  pair  denotes  the 
degree  of  reaction  in  the  front  tube,  and  the  right- 
hand  symbol  that  in  the  corresponding  back-row  tube, 
the  five  degrees  of  reaction  mentioned  above  will  be 
recorded  respectively — 

+  +,  +±,  +-,  ±-,  -  -. 

It  is  obvious  that  a  quantitative  measurement  for 
the  complement-fixation  substance  in  the  serum  can 


76  SYPHILIS  AND  PARASYPHILIS 

be  made  either  by  using  varying  quantities  of  com- 
plement, keeping  the  other  factors  constant,  as  above 
described  ;  or  by  varying  the  quantity  of  antigen, 
keeping  the  complement  and  test-serum  constant ;  or 
by  altering  the  quantity  of  test-serum,  keeping  the 
antigen  and  complement  constant.  The  author  finds 
that  the  greatest  range  is  obtained  when  the  quantity 
of  the  serum  is  altered ;  but,  if  to  be  of  value,  at  least 
five  dilutions  must  be  made,  and  this  takes  a  con- 
siderable time,  and  therefore  the  author  only  employs 
this  method  in  doubtful  cases.  If  a  serum  is  strongly 
positive,  it  will  appear  so  by  both  methods,  and  will 
by  the  first  one  fix  a  large  amount  of  complement,  or 
by  the  second  will  fix  complement  when  the  serum  is 
present  only  in  very  small  quantities. 

Quantitative  Measurement  by  Variation  in 
Amount  of  Test-Serum. 

In  the  second  method  the  ingredients  are  used 
in  the  same  proportion  as  in  the  front  row  of  the 
first  method — namely,  i  c.c.  saline,  0*05  c.c.  com- 
plement, and  o'l  c.c.  antigen.  Five  tubes  are 
required  for  each  serum  to  be  tested,  each  contain- 
ing the  above  quantity  of  saline,  complement,  and 
antigen,  and  dilutions  of  the  serum  are  prepared 
in  the  following  way :  f  c.c.  saline  is  put  into 
four  small  test-tubes,  ^  c.c.  serum  added  to  the  first ; 
this  is  shaken,  and  J  c.c.  put  into  the  next  tube, 
and  so  on.  In  this  way  dilution  of  i  in  2,  i  in  4, 
I  in  8,  and  i  in  16  are  obtained.  0*2  c.c.  of  the  pure 
serum  and  0-2  c.c.  of  each  dilution  are  added  to  the 
tubes   of  saline,    complement,   and   antigen.      These 


WASSERMANN  REACTION  77 

tubes  will  thus  contain  0*2,  o*i,  0-05,  0-025,  0-0125^  of 
test-sernm  respectively.  It  will  be  found  that  the 
smallest  amount  in  this  series  is  capable  of  producing 
complete  inhibition  of  haemolysis  with  a  very  strong 
serum.  This  potency  of  the  serum,  however,  is  rare, 
and  a  serum  is  definitely  syphilitic  when  it  fixes  com- 
plement completely  in  the  0-2  or  o'l  c.c.  tubes. 
Sometimes  a  case  will  be  found  gradually  to  come 
down  in  complement-fixing  power,  from  at  first  being 
able  to  fix  complement  in  all  the  tubes  up  to  the  last 
tube,  until  the  first  tube  alone  is  fixed,  then  only 
partially  fixed,  and  at  last  all  the  tubes  show  complete 
haemolysis.  The  author  considers  this  method  of 
making  a  quantitative  examination  the  most  satis- 
factory ;  but  as  the  results  obtained  by  the  two 
methods  always  agree,  the  longer  process  is  unneces- 
sary in  the  majority  of  cases,  and  need  only  be  used 
for  the  more  accurate  estimation  of  improvement 
under  treatment. 

Quantitative  Measurement  when  only  a  Small 
Amount  of  Blood  is  Available. 

Occasionally,  as  in  infants  or  fat  persons,  veni- 
puncture is  impossible,  and  the  pathologist  has  to 
content  himself  with  a  small  quantity  of  blood 
obtained  from  the  finger  or  toe  in  a  Widal  tube. 
In  these  cases  we  have  to  modify  the  technique  as 
regards  the  quantity  of  serum  used,  though  not  as 
regards  the  relative  proportion  of  the  ingredients. 

A  piece  of  glass  tubing  having  been  heated  in  a 
blowpipe  and  drawn  out  so  as  to  form  a  pipette,  the 
capillary  portion  of  which  is  about  6  inches  long,  a 


7S  SYPHILIS  AND  PARASYPHILIS 

mark  is  made  with  a  pencil  about  i  inch  from  the 
end  of  the  capillary  portion  to  mark  one  volume.  A 
rubber  teat  having  been  adjusted  to  the  broad  end  of 
the  pipette,  the  mixture  of  saline,  antigen,  and  com- 
plement is  sucked  up  to  the  chalk  mark  ;  the  point  of 
the  pipette  is  then  taken  out  of  the  fluid  and  a  little 
air  drawn  in,  and  then  another  volume  is  drawn  in  up 
to  the  mark,  and  so  on  until  seven  volumes  have  been 
sucked  up.  These  are  then  squeezed  out  into  a  clean 
watch-glass  and  again  sucked  up,  this  time  without 
leaving  any  intervening  air-bubbles,  and  a  chalk  mark 
made  on  the  capillary  at  the  point  to  which  the 
mixture  reaches  (Fig.  19).     A  small  air-bubble  is  now 


Fig.  19.  — Teat-Pipette,  marking  One  and  Seven  Volumes. 

admitted  into  the  capillary,  and  then  one  volume  of 
the  serum  to  be  tested  is  sucked  up.  The  contents 
of  the  pipette  are  then  ejected  into  a  front-row  test- 
tube  of  small  bore,  made  by  drawing  out  glass  tubing. 
The  pipette  is  then  washed  by  sucking  up  and  ejecting 
normal  saline  one  or  twice,  and  the  same  process 
repeated— on  this  occasion,  however,  sucking  up  the 
mixture  v/ith  the  triple  quantity  of  complement  to  the 
7-volume  mark,  and  then  ejecting  it  into  a  test-tube 
in  the  back  row.  The  same  technique  is  followed 
with  each  serum  to  be  tested,  and  with  the  controls. 
We  have,  as  before,  two  rows,  the  front  row  contain- 
ing a  third  of  the  amount  of  complement  contained  in 
the  back  row,  the  only  difference  being  the  absolute 


WASSERMANN  REACTION  79 

quantities  used,  relative  amounts  being  practically  the 
same. 

After  incubating  for  half  an  hour,  eight  volumes  of 
haemolytic  system  are  added,  and  the  tubes  replaced  in 
the  incubator  until  complete  haemolysis  occurs  in  the 
control-tubes  containing  normal  serum  and  no  serum. 

Reasons  for  Superiority  of  Original  Technique. 

It  will  be  seen  that  the  same  principle  underlies 
all  the  above  techniques  —  namely,  that  all  the 
factors  are  constant,  except  the  test-serum.  Any 
difference  in  haemolysis  must  therefore  be  due  to  this, 
the  only  variant  factor,  and  the  results  obtained  will 
be  strictly  comparable  one  with  another,  though  not 
strictly  comparable  to  another  series  of  tests.  Thus, 
if  in  any  given  experiment  the  guinea-pig's  serum 
is  rather  deficient  in  complement,  or  contains  com- 
plement that  is  easily  deviable,  perhaps  not  quite 
complete  haemolysis  will  be  produced  in  the  tubes 
containing  normal  sera.  The  test-tubes  showing  a 
similar  amount  of  haemolysis  we  may  then  report  as 
normal,  although  complete  haemolysis  is  not  produced. 
Or,  again,  if  we  use  an  excessively  potent  complement, 
there  may  be  a  trace  of  haemolysis  even  in  the  tube 
containing  syphilitic  serum  ;  all  the  test-tubes  showing 
a  similar  trace  of  haemolysis,  we  may  then  report  as 
positive.  It  cannot  be  too  strongly  insisted  upon  that 
this  test  is  a  quantitative  one,  and  not  an  absolute 
one,  and  that  therefore  a  result  which  in  one  test  we 
should  report  as  doubtful  may  in  another  test  be 
reported  as  either  positive  or  negative,  according  to 
the  results  obtained  from  the  control-tubes. 


8o  SYPHILIS  AND  PARASYPHILIS 

Strictly  comparable  results  cannot  be  claimed  for 
any  of  the  so-called  *  simplified  methods '  given  in  the 
next  chapter. 

The  author  has  always  urged  the  importance  of 
maintaining  the  principle  of  Wassermann's  and 
Neisser's  original  technique,  and  nearly  all  patholo- 
gists with  an  extensive  experience  of  the  Wassermann 
reaction  (Wassermann,  Neisser,  Plant,  Noguchi, 
Harrison,  Macintosh,  Browning,  Mackenzie)  now 
advise  that  only  a  technique  embodying  these  prin- 
ciples is  to  be  recommended  for  purposes  of  diagnosis. 
Practically  every  worker  of  experience  has  his  own 
modifications.  These,  however,  are  immaterial  so 
long  as  the  original  principles  are  adhered  to — namely, 
the  only  variant  factor  shall  be  the  test-serum,  and 
that  the  results  in  any  one  series  of  tests  shall  be 
strictly  comparable. 

The  technique  employed  by  the  workers  at  the 
Lister  Institute,  and  by  Mott  and  Candler  in  the 
Pathological  Laboratory  at  Claybury  Asylum,  is  the 
original  one.  General  experience  has  shown  that  this 
method  is  by  far  the  most  reliable,  and  admits  of 
more  accurate  standardization  than  do  any  of  the 
labour-saving  modifications  which  have  been  suggested 
as  substitutes  for  the  original  method. 


CHAPTER  VII 

WASSERMANN  RR ACTION— Continued 

SIMPLIFIED  TECHNIQUES 

I.  Stern's  Method. — Margaret  Stern  makes  use  of 
normal  complement  existing  in  the  serum  tested  instead 
of  using  guinea-pig's  complement.  This  considerably 
simplifies  the  reaction  in  that  guinea-pigs  are  not 
required,  and  the  test-serum  is  not  decomplementized 
in  the  water  -  bath.  The  quantity  of  complement 
contained  in  human  sera  is  very  variable.  Comple- 
ment is  also  gradually  destroyed  by  keeping.  As  each 
serum  tested  varies,  therefore  in  the  quantity  of  comple- 
ment, and,  unless  all  are  drawn  on  the  same  day,  the 
depreciation  of  complement  produced  by  time  is  also 
variable,  the  results  obtained  by  this  method  are  not 
quite  comparable.  In  order  to  minimize  the  variability 
in  complement,  Stern  advises  using  a  large  excess  of 
haemolytic  serum,  and  only  a  weak  suspension  of 
corpuscles  (2-5  per  cent.).  Although  satisfactory 
results  are  obtained  by  this  method  in  the  very  large 
majority  of  cases,  still  there  is  undoubted  evidence 
from  records  published  by  independent  observers  in 
many  countries  that  with  this  technique  positive 
results  are  sometimes  recorded  in  diseases  other  than 

81  6 


82  SYPHILIS  AMD  PARASYPHILIS 

syphilis,  and  there  is  practically  always  a  higher 
percentage  of  positive  results.  Stern  herself  admits 
that  her  method  is  not  reliable  in  wasting  diseases, 
where  there  may  be  a  deficiency  of  complement. 
There  is  little  doubt  but  that  Stern's  method  is  more 
delicate  than  Wassermann's  original  technique,  and 
Harrison  makes  use  of  this  method  when  estimating 
the  result  of  treatment  on  the  reaction,  although  he  is 
strongly  of  the  opinion  that  Stern's  modification  is 
unsuitable  for  diagnostic  purposes.  Neisser  considers 
this  technique  useful  as  a  control  of  the  original 
technique. 

2.  Hecht's  Method. — This  observer  uses  the  test- 
serum  not  only  for  complement,  as  in  Stern's  method, 
but  also  for  haemolytic  antibody,  for  he  has  shown  that 
an  antibody  to  sheep's  corpuscles  is  present  in  the 
great  majority  of  human  sera.  The  author  compared 
the  results  obtained  with  Hecht's  technique  and  the 
original  technique  with  one  hundred  sera,  and  found 
that  lo  per  cent,  of  human  sera  contained  no,  or  very 
little,  haemolytic  antibody  to  sheep's  corpuscles,  and 
that  therefore  lo  per  cent,  of  human  sera  cannot  be 
examined  with  this  technique,  and  of  the  remaining 
90  per  cent,  the  author  found  a  higher  proportion  of 
positives  than  with  the  original  technique.  Hecht 
emphasizes  the  importance  of  using  only  fresh  serum. 
Flemming  has  adapted  a  capillary  tube  method  of 
measurement  to  this  technique,  and  his  modification 
has  been  considerably  used  in  this  country  :  he  states 
that  the  freshness  of  the  serum  is  not  of  importance, 
and  that  satisfactory  results  are  obtained  even  if  the 
serum  is  a  week  old.     Little   can   be   said   for  this 


WASSERMANN  REACTION  83 

technique  on  theoretical  grounds,  as  both  complement 
and  haemolytic  antibody  are  variants,  and  variations 
in  haemolysis  may  be  due  not  only  to  varying 
quantities  in  the  complement-fixing  substance  present 
in  syphilitic  sera,  but  to  deficiency  in  either  comple- 
ment, haemolytic  antibody,  or  both. 

3.  Noguchi's  Method. — Noguchi,  according  to  his 
latest  method,  endeavours  to  simplify  the  reaction 
by  substituting  human  corpuscles  for  the  sheep's 
corpuscles,  using  the  patient's  own  corpuscles,  acetone 
insoluble  antigen,  and  fresh  guinea-pig's  complement. 
The  corpuscles,  after  washing,  are  used  in  a  strength 
of  I  per  cent,  suspension.  The  controls  consist  of 
syphilitic  serum,  normal  serum,  and  a  tube  without 
antigen.  The  decomplementized  patient's  serum,  the 
patient's  washed  corpuscles,  the  fresh  guinea-pig's 
serum  for  complement,  and  the  antigen  are  incubated 
together  in  a  water-bath  for  half  an  hour.  The  serum 
haemolytic  to  human  corpuscles  is  now  added,  and  the 
tubes  are  reincubated. 

SOURCES  OF  ERROR 

The  dose  of  complement  in  different  samples  of 
different  guinea-pig's  serum,  though  more  constant 
than  in  human  serum,  still  may  vary,  and  Browning 
and  Mackenzie  have  shown  that  different  samples 
of  guinea-pig's  complement  may  vary  considerably 
also  in  deviability,  and  this  deviability  is  particularly 
influenced  by  age  ;  they  found  that  the  comple- 
ment of  freshly  drawn  serum  was  hypersensitive 
in  deviability,  and  considered  it  best  that  comple- 
ment should   be  kept   from  eighteen  to  twenty-four 


84  SYPHILIS  AND  PARASYPHILIS 

hours  in  the  ice- chest,  or  at  room  temperature,  before 
use.  They  consider  that  complement  is  hyper- 
sensitive if  five  times  the  quantity  of  complement 
is  required  to  produce  haemolysis  with  antigen, 
corpuscles,  and  haemolytic  serum,  than  with  corpuscles 
and  haemolytic  serum  alone. 

From  the  above  remarks  it  will  be  seen  that  there 
are  numerous  pitfalls  open  to  those  inexperienced  in 
the  technique  when  using  any  of  the  so-called 
'  simplified  techniques.' 

When  using  either  Stern's  or  Hecht's  technique,  or 
Flemming's  modification  of  Hecht's  technique,  it  is 
obviously  impossible  to  make  a  quantitative  examina- 
tion, as  we  are  unable  to  increase  the  amount  of  com- 
plement-fixing substance  which  is  being  tested  for  in 
the  patient's  own  serum,  without,  at  the  same  time, 
increasing  the  complement,  and  with  Hecht's  the 
haemolytic  antibody  also.  With  cerebro-spinal  fluid 
these  techniques  cannot  be  used. 

Reliable  quantitative  estimation  can  alone  be  made 
by  using  the  original  method,  in  which  the  patient's 
own  serum  or  cerebro-spinal  fluid  is  simply  used  for 
supplying  the  complement  -  fixing  substance.  The 
quantitative  measurement  may  be  arrived  at  by  giving 
increasing  or  diminishing  doses  of  either  of  three  factors 
— namely,  either  complement,  antigen,  or  test-serum. 
It  will  be  seen  that  false  results  may  be  obtained  : 

1.  By  the  use  of  fresh  guinea-pig's  serum  contain- 
ing abnormally  little  or  abnormally  much  complement ; 
by  using  too  much  complement  or  complement  which 
is  too  easily  deviable  or  not  sufficiently  deviable. 

2.  By  using  antigen  which  is  too  potent  or  not 
sufficiently  potent ;   one  which  fixes  too  much  comple- 


WASSERMANN  REACTION  85 

ment  by  itself,  or  with  normal  serum ;  or  one  in 
which  the  units  of  complement  fixed  in  conjunction 
with  syphilitic  serum  are  not  sufficiently  in  excess  of 
those  fixed  in  conjunction  with  normal  serum. 

3.  Some  corpuscles,  also,  are  more  easily  haemo- 
lyzed  than  others  ;  or,  again,  if  too  thick  a  suspension 
of  corpuscles  be  employed,  there  may  not  be  complete 
haemolysis,  even  with  normal  sera,  while,  if  the 
suspension  is  too  weak,  each  corpuscle  will  be  pro- 
vided with  an  excess  of  hsemolytic  serum,  and 
haemolysis  will  be  produced  with  a  minimum  amount 
of  complement  that  would  fail  to  produce  haemolysis  in 
a  thicker  suspension. 

4.  The  haemolytic  serum,  if  too  potent,  will  for  the 
same  reason  produce  haemolysis,  and  if  too  weak  the 
serum  will  have  to  be  used  in  such  large  quantities 
that  agglutination  of  the  corpuscles  may  be  produced, 
and  the  clumps  fall  to  the  bottom  of  the  test-tube 
before  they  are  dissolved. 

5.  The  patient's  serum,  if  not  decomplementized, 
may,  according  to  Neisser,  Noguchi,  and  others,  fix 
complement,  even  if  non-syphilitic,  or  if  decomple- 
mentized at  too  high  a  temperature,  or  for  too  long, 
the  complement -fixing  substance  may  be  greatly 
reduced  in  quantity,  or  even  destroyed. 

For  this  reason  none  of  the  outfits  supplied  by 
instrument  makers  can  be  regarded  as  satisfactory. 
The  accumulated  evidence  of  responsible  workers 
points  unmistakably  to  the  superiority  of  the  original 
technique  in  which  the  only  variant  factor  is  the 
tested  serum,  and  any  variation  in  haemolysis  in  the 
final  tubes  must  therefore  be  due  to  this  the  only 
variant  factor. 


CHAPTER  VIII 

WASSERMANN   REACTION— Contimied 

SPECIFICITY  OF  REACTION 

The  first  question  to  be  settled  is  whether  the  reaction 
is  sufficiently  specific  to  render  the  test  a  reliable  one 
for  the  diagnosis  of  syphilitic  infection.  Wassermann 
states  that  out  of  10,000  sera  examined,  he  has  not 
once  diagnosed  syphilis  wrongly,  and  Hoehne  only 
obtained  two  positive  results  out  of  1,100  sera  taken 
from  healthy  persons,  or  patients  sufiering  from 
diseases  other  than  syphilis,  and  in  neither  of  these 
two  could  syphilis  be  excluded.  McDonagh,  Muller, 
and  Morawitz,  in  reporting  5,000  cases  examined  by 
them  in  Finger's  clinic,  state  that  they  did  not  obtain 
a  single  positive  result  in  any  case  where  syphilis 
could  be  definitely  excluded  ;  and  Blaschko  of  BerHn, 
as  the  result  of  the  examination  of  900  cases,  found 
the  result  in  accordance  with  the  clinical  diagnosis  in 
all  but  30  cases. 

Blumenthal  found  in  3,000  cases  a  positive  reaction 
in  95  per  cent,  of  secondary  and  tertiary  cases.  There 
was  no  relation  to  the  duration  and  the  gravity  of  the 
disease.  Congenital  syphilis  behaved  in  just  the 
same  way  as  acquired  syphilis.     Of  400  control  cases 

86 


WASSERMANN  REACTION  87 

5  only  gave  a  positive  reaction.  In  latent  syphilis 
the  reaction  was  positive  in  68  per  cent,  of  cases  in 
the  first  year  of  the  disease,  and  in  42  per  cent,  of 
cases  afterwards. 

Fritz  Hoehne  found  that  of  317  known  non-syphilitic 
cases  only  3  were  positive,  and  in  2  of  these  syphilis 
could  not  be  absolutely  excluded,  and  i  was  a  case 
of  scarlet  fever. 

Koefting,  R.,  of  Christiania,  obtained  100  per  cent, 
of  positive  results  out  of  317  secondary  cases  examined ; 
and  of  426  non-syphilitic  cases  all  were  negative. 

Markus,  K.,  of  Stockholm,  records  374  positive 
reactions  in  445  cases  of  syphilis  examined,  and 
9  out  of  338  cases  diagnosed  as  non-syphilitic,  but 
out  of  these  9,  in  7  syphilis  could  not  be  excluded, 
and  the  remaining  2  consisted  of  typhoid  and  tuber- 
cular meningitis. 

Out  of  50  sera  examined  by  Beckers,  and  taken 
from  patients  with  tuberculosis,  typhoid,  scarlet  fever, 
arterio- sclerosis,  and  heart  failure,  only  2  gave  a 
positive  reaction,  in  neither  of  which  syphilis  could 
be  excluded. 

Jenonck  and  Meirowski  examined  no  certainly 
non-syphilitic  cases,  and  only  found  i  positive  result, 
which  was  that  of  a  child  dying  with  tuberculous 
meningitis,  and  they  and  other  observers  have 
recorded  that  a  positive  result  is  often  obtained  with 
dying  persons  or  cadavers. 

Statistics  taken  from  very  many  thousands  of  obser- 
vations made  by  skilled  workers  in  England,  France, 
Germany,  Austria,  Sweden,  America,  and  Australia, 
show  that   of   all    cases  of   syphilis  examined,   from 


88  SYPHILIS  AND  PARASYPHILIS 

80  to  90  per  cent,  give  a  positive  reaction.  The 
percentage  differs  but  slightly  with  different  observers. 
The  author  has  determined  the  reaction  in  over  500 
untreated,  or  but  slightly  treated,  cases,  and  obtained 
a  positive  reaction  in  85  per  cent.,  and  out  of  over  3,000 
sera  personally  examined  by  him  has  not  recorded  a 
single  positive  reaction  in  any  case  in  which  syphilis 
could  be  excluded,  with  the  exception  of  a  few  post- 
critical  pneumonias. 

Different  results  are  obtained  with  syphilitic  lesions 
of  different  tissues;  thus  a  very  high  percentage  of 
positive  results  is  obtained  with  aneurism  of  the  aorta, 
and  only  a  low  percentage  with  cerebral  syphilis. 

REACTIONS  IN  CONDITIONS  OTHER  THAN 
SYPHILITIC 

Of  the  diseases  certainly  not  syphilitic  in  which  a 
positive  reaction  is  obtained — 

Yaws  heads  the  list,  and  in  this  disease  as  high  a 
proportion  of  positives  is  obtained  as  with  syphiHs 
itself.  Baermann  obtained  90  per  cent,  of  positives 
in  untreated  cases. 

Leprosy  also  produces  a  high  percentage  of  positive 
results,  Baermann  reporting  40  per  cent,  and  Noguchi 
80  per  cent.  Meier  also  reported  that  the  majority  of 
cases  gives  a  strongly  positive  result.  It  appears, 
however,  only  to  be  the  tuberculous  form  of  the 
disease  that  produces  a  positive  reaction. 

Trypanosomiasis  has  been  reported  frequently  to  give 
a  positive  reaction,  but  the  author  has  been  unable  to 
obtain  any  statistics  for  the  reaction  in  this  disease. 

In  malaria  Baermann  obtained  20  per  cent,  positive 


WASSERMANN  REACTION  89 

in  untreated  cases  with  fever,  and  4  per  cent,  positive 
in  treated  cases  without  fever. 

Scarlet  fever  was  at  first  beheved  to  produce  a 
positive  reaction,  and  Much  reported  59  positives  out 
of  130  cases  examined.  Later  observers  have,  how- 
ever, failed  to  confirm  his  figures,  and  have  only 
obtained  positive  results  very  rarely.  In  any  case 
the  positive  reaction  is  said  to  be  very  transient,  and 
Blaschko  has  observed  that  when  the  positive  result 
does  occur,  it  is  not  till  about  fourteen  days  after  the 
rash  that  it  appears,  and  that  it  disappears  within 
three  months  (see  Table  I.). 

Pnetimonia. —  Weil  and  Braun  and  the  author  have 
reported  36  cases  of  pneumonia  in  which  a  positive 
reaction  was  obtained  in  11.  The  author  found  that 
the  positive  reaction  did  not  appear  till  after  the  crisis, 
and  only  lasted  a  few  days. 

Weil  and  Braun  have  also  reported  3  positive 
results  out  of  20  sera  taken  from  typhoid  patients 
(see  Table  I.). 

Heart  Disease. — No  case  of  heart  disease  in  which 
syphilis  can  be  excluded  has  been  reported  as  giving 
a  positive  reaction. 

Relapsing  fever  has  been  reported  as  giving  a  positive 
reaction. 

Cancer  or  tuberculosis  practically  never  gives  a  positive 
reaction  in  cases  in  which  syphilis  can  be  excluded. 
The  reports  of  some  experienced  observers  as  regards 
the  reaction  in  various  diseases  will  be  found  in  Table  I. 

Reinhart  has  not  obtained  a  single  positive  result 
in  malignant  disease,  phthisis,  typhoid,  pneumonia, 
nephritis,    leukaemia,    pernicious    anaemia,    diabetes, 


90  SYPHILIS  AND  PARASYPHILIS 

measles,  or  diphtheria,  but  he  has  recorded  positive 
reactions  in  scarlet  fever  and  malaria. 

Of  39  cases  of  various  non-syphilitic  skin  diseases 
examined  by  Bassett- Smith,  all  gave  a  negative 
reaction.  Of  58  examined  by  Noguchi,  all  but  i  were 
negative,  this  solitary  case  giving  a  doubtful  reaction. 
Of  15  cases  examined  by  the  author,  10  gave  a  nega- 
tive reaction,  and  5  cases — all  leucoderma  cervices 
and  probably  syphilitic — gave  a  positive  reaction. 

Positive  reactions  have  also  been  recorded  with 
blood  taken  during  deep  anaesthesia,  or  in  narcosis  pro- 
duced by  various  drugs ;  also  in  moribund  patients  and 
in  the  cadaver. 

Of  80  cases  of  gonorrhoea  examined  by  Bassett-Smith 
and  the  author,  only  i  was  positive,  and  here  syphilis 
could  not  be  excluded. 

Acute  rheumatism,  measles,  and  acute  nephritis 
have  all  given  negative  results. 

Of  76  cases  of  aortic  aneurism  examined  by  Donath, 
Gastau,  Koefting,  and  the  author,  all  but  4  have  given 
a  positive  reaction.  Koefting  also  obtained  15  positive 
reactions  out  of  17  cases  of  aortic  incompetence,  but 
out  of  21  cases  of  morbis  cordis  examined  by  Bassett- 
Smith  and  the  author,  only  i  gave  a  positive  reaction, 
and  here  there  was  a  history  of  syphilis. 

Wassermann  says : 

'  It  should  cause  no  surprise  that  the  serum  of 
patients  suffering  from  other  protozoal  diseases  gives 
a  like  reaction,  considering  the  close  relationship 
between  spirochaetse,  trypanosomes,  and  other  pro- 
tozoa. It  follows  that  one  should  employ  the  reaction 
with  people  who  have  been  in  the  tropics  and  con- 
tracted malaria  there,  only  when  one  is  convinced  by 


WASSERMANN  REACTION 


91 


their  history  that  they  have  had  no  malarial  attack 
during  the  last  quarter  of  a  year.  I  also  advise  you 
that  whenever  you  wish  to  employ  the  serum  reaction 
first  to  determine  by  the  patient's  history  that  he  has 
gone  through  no  acute  febrile  infectious  disease  up  to 
at  least  a  month  previously.  If  one  holds  to  the 
necessary  preliminary  precautions  regarding  the  tech- 
nique and  the  anamnesis,  then,  in  cases  of  a  positive 
reaction,  it  can  be  said  with  certainty  that  the  investi- 
gated case  is  syphilitic.  On  the  other  hand,  if  the 
reaction  be  negative,  syphilis  cannot  be  excluded 
absolutely,  but  only  with  a  probability  of  about 
90  per  cent.' 

Table  I. — Reaction  in  Various  Diseases. 


Typhoid. 

Scarlet 
Fever. 

Tuber- 
culosis. 

Carcinoma. 

Pneumonia. 

Cases. 

No. 
Posi- 
tive. 

Cases. 

No. 
Posi- 
tive. 

Cases. 

No. 
Posi- 
tive. 

Cases. 

No. 
Posi- 
tive. 

Cases. 

No. 
Posi- 
tive. 

Bassett-Smith 
Bayly 
Boas  . . 
Browning  and 

Mackenzie 
Hecht 
Hoehne 
Jochmann    .. 
Meier 
Much 
Noguchi 
Weil    and 

Braun 

3 
6 

14 
20 

0 
0 

0 
3 

7 
20 
61 

37 
105 
37 
33 
52 
130 

63 

I 
I 
I 

0 
I 
0 
0 
0 
59 
3 

9 
22 

II 

52 

0 
0 

I 
0 

34 
5 

5^ 

0 
0 

3 

24 
4 

12 

7 
0 

4 

REACTION  AT  VARIOUS  STAGES  OF 
INFECTION 

The  percentage  of  positive  reactions  obtained  varies 
considerably  with  the  period  of  the  disease,  and  whether 


92  SYPHILIS  AND  PARASYPHILIS 

the  infection  is  acute  or  latent.  Thus,  primary  cases 
in  which  the  lesion  has  been  present  for  less  than  a 
fortnight  almost  invariably  give  a  negative  reaction, 
while  75  per  cent,  of  positive  reactions  are  obtained  if 
the  primary  sore  has  been  present  for  over  a  month. 
Secondary  syphilis  v/ith  symptoms  gives  a  positive 
result  in  over  90  per  cent,  of  cases,  and  tertiary 
syphilis  in  about  75  per  cent.  In  cases  of  latent 
syphilis — viz.,  syphilis  without  symptoms — the  early 
cases  give  a  positive  reaction  in  75  per  cent,  and  the 
late  cases  in  76  per  cent.,  in  the  untreated  cases. 

Primary  Syphilis  (see  Table  II.). — Levaditi  and 
Yamanouchi  found  a  positive  reaction  in  primary 
cases  in  from  ten  to  thirty  days  after  the  appearance 
of  the  sore. 

Bruck  and  Boas  collected  records  of  1,081  cases  of 

primary  syphilis,  and  of  these  709,  or  65  per  cent., 

gave  positive  reactions. 

Fischer  found  a  positive  result  the  rule  after  five  or 

six  weeks. 

Blumenthal  found  a  positive  reaction  in  the  primary 

period  in  63  per  cent,  of  cases.     It  only  appeared  in 

the  fifth  or  sixth  week,  and  became  more  and  more 

strong   as    time    progressed.      In   other   periods   the 

reaction  was  positive. 

Secondary  Syphilis  (see  Table  II.). — Bruck  and 

Boas   obtained   90   per   cent,   of    positive   results   in 

2,754  cases.     Probably,  however,  many  of  these  had 

received  some  treatment. 

Recent  observations  seem  to   show  that  in  florid 

secondary    syphilis    practically    every   case    gives    a 

positive  reaction. 


WASSERMANN  REACTION  93 

Tertiary  Syphilis  (see  Table  II.).  —  In  63  un- 
treated cases  recorded  by  Boas,  every  case  gave  a 
positive  reaction,  and  in  60  cases  examined  by  Mac- 
intosh and  Fildes,  only  i  negative  result  was 
obtained. 

Very  many  cases  of  aneurism  of  the  aorta  give  a 
positive  reaction,  and  in  the  majority  a  history  of 
syphilis  can  also  be  obtained.  Bassett-Smith  has  in- 
formed the  author  that  in  his  report  on  late  secondary 
and  tertiary  syphilis  giving  positive  reactions,  he 
included  many  cases  of  aneurism,  chronic  endo- 
carditis, and  cases  with  cerebral  symptoms  in  which 
a  distinct  history  of  syphilis  had  been  obtained. 

Congenital  Syphilis  (see  Table  11.). — Practically 
all  infants  or  children  showing  symptoms  of  hereditary 
syphilis  give  a  positive  reaction,  but  not  all  babies 
born  of  syphilic  mothers ;  while  of  living  children 
born  of  syphilitic  mothers  nearly  50  per  cent,  give  a 
negative  reaction. 

Of  44  cases  examined  by  Boas,  20  gave  a  positive 
reaction  and  24  a  negative ;  of  the  20  that  gave  a 
positive  reaction,  16  either  showed  symptoms  at  birth 
or  within  three  months  after  birth,  and  the  remaining 
4  showed  no  symptoms  in  three  months,  and  the 
reaction  rapidly  became  negative.  Of  the  24  cases 
showing  a  negative  reaction,  17  remained  negative 
and  showed  no  symptoms,  5  developed  both  symptoms 
and  a  positive  reaction,  and  2  died  with  a  negative 
reaction  and  yet  proved  to  be  syphilitic. 

Knopfelmacher  obtained  90  per  cent,  of  positive 
reactions  in  mothers  tested  within  a  few  months  after 
the  birth  of  a  syphilitic  child,  and  he  has  shown  that 


94  SYPHILIS  AND  PARASYPHILIS 

children  with  hereditary  syphilis  almost  invariably 
give  a  positive  Wassermann  reaction  at  the  time  of 
the  rash  and  often  for  long  after  its  disappearance. 
Older  children  with  hereditary  syphilis  show  a  positive 
reaction  even  more  frequently  than  adults  with  acquired 
syphilis  in  a  late  stage,  and  the  reaction  often  remains 
positive  in  children  suffering  from  the  disease  in  spite 
of  energetic  treatment.  That  antisyphilitic  treatment 
of  the  mother  during  pregnancy  can  result  in  the  birth 
of  a  healthy  child  is  confirmed  by  the  negative  reaction. 
These  children  are  free  from  syphilis,  and  they  may 
be  quite  healthy  or  show  various  defects.  In  two 
instances  a  woman,  who  had  previously  had  several 
syphilitic  children,  has  borne  a  child  which  has  re- 
mained healthy  in  the  first  years  of  life,  and  yet  given 
a  positive  Wassermann  reaction.  Such  children  are 
to  be  regarded  as  latent  syphilitics.  On  this  basis 
Profeta's  law  (immunity  of  the  healthy  children  of 
syphilitic  mothers)  finds  its  explanation  on  the  ground 
of  latent  syphilis  in  the  child. 

Out  of  1,822  sera  Fritz  Hoehne  obtained  positive 
reactions  in : 

38  per  cent,  in  primary  syphilis. 


79 

,      untreated  secondary  syphili 

48 

,      treated  secondary  syphilis. 

63 

tertiary  syphilis. 

100 

,      syphilitic  aortitis. 

17 

cerebro-spinal  syphilis. 

31 

,      latent  syphilis. 

88 

,      congenital  syphilis. 

60 

tabes. 

Of  427  doubtful  cases,  loi  were  positive. 


WASSERMANN  REACTION 


95 


Table    II. — Reaction    at    Different    Stages    of 
Infection  in  Cases  showing  Clinical  Symptoms. 


England. 

America. 

Germany. 

Sweden. 

Bassett- 
Sniith. 

Bayly. 

Noguchi 

and 
Kaplan. 

Hoe 

tine. 

Markus. 

Boas. 

cS 

U 

it 

u.-a 

-I 

0 

u5 
0 

u.t: 

o.t: 

1) 
(J 

t-  0 

Congeni- 

tal      .. 

— 



20 

QS 

3,7 

QS 

? 

88 

29 

90 

72 

100 

Primary 

183 

76 

^B 

7,S 

208 

QO 

? 

3a 

120 

75 

7fc 

73 

Second- 

ary   . . 

407 

Q4 

308 

qo 

478 

QO 

? 

79 

250 

91 

2,754 

90 

Tertiary 

51 

94 

52 

76 

363 

80 

9 

63 

45 

100 

63 

100 

CHAPTER  IX 
CEREBRO-SPINAL  FLUID 

The  normal  cerebro-spinal  fluid  is  limpid  and  colour- 
less, and  has  a  specific  gravity  of  1005  5  i^  contains 
no  cellular  element,  except,  perhaps,  a  few  large 
endothelial  cells  and  a  very  occasional  lymphocyte, 
and  its  reaction  is  slightly  alkaline.  True  albumin 
is  absent.  Only  faint  traces  of  proteid  are  present, 
which,  however,  are  sufficient  to  produce  a  slight 
cloudiness  on  heating.  The  proteid  present  consists 
of  globulin.  No  ferments  can  be  demonstrated.  Of 
salts,  the  principal  is  sodium  chloride,  but  it  also  con- 
tains traces  of  carbonates  and  phosphates.  Traces  of 
dextrose  and  urea  are  also  usually  found. 

From  120  to  150  c.c.  of  cerebro-spinal  fluid  are 
usually  secreted  daily,  the  secretion  being  produced 
at  the  choroid  fringes,  and  being  a  definite  secretion 
and  in  no  sense  an  exudation.  The  amount  secreted 
varies  in  pathological  conditions,  and  may  be  enor- 
mously increased  in  general  paralysis. 

Hoffman  states  that  he  has  been  able  to  demon- 
strate the  presence  of  the  SpirochcBta  pallida  in  the 
cerebro-spinal  fluid  of  infected  persons  by  means  of 
successful  inoculation,  but  the  organism  itself  has  up 
till  now  not  been  seen  in  this  fluid. 

96 


CEREBROSPINAL  FLUID  97 

LUMBAR  PUNCTURE 

Cerebro-spinal  fluid  is  best  obtained  by  thecal 
puncture  at  the  interlaminal  spaces,  either  between 
the  third  and  fourth  or  fourth  and  fifth  lumbar 
vertebrae.  The  upper  border  of  the  fourth  lumbar 
spine  is  on  a  level  with  a  horizontal  line  joining  the 
summit  of  the  iliac  crests,  and  the  puncture  should  be 
made  below  this  line,  ^  inch  below  and  to  the  right 
of  the  fourth  lumbar  spine,  directing  the  needle 
forwards  and  inwards. 


Fig.  20. — Lumbar  Puncture  Needle  and  Holder  (Author's 

Pattern), 

A,  holder ;  B,  needle  ;  C,  stilette  ;  D,  rubber-tubing. 

Before  puncture,  the  skin  should  be  cleaned  with 
ether  and  alcohol,  and  sterilized  with  a  saturated 
solution  of  iodine  in  chloroform.  The  needle  is  often 
attached  to  the  nozzle  of  a  syringe.  Most  authorities 
agree  that  suction  should  not  be  employed,  and  there- 
fore the  syringe  usually  serves  only  as  a  handle. 

The  author  uses  the  apparatus  illustrated  in  Fig.  20, 
which  consists  of  a  stout  steel  needle,  about  3  inches 
long  and  of  fairly  large  calibre,  and  a  hollow  needle- 
holder   to   which   a   piece    of    rubber-tubing   can  be 

7 


98  SYPHILIS  A ND  PA  RA  SYPHILIS 

attached  so  that  the  cerebro-spinal  fluid  is  conducted 
directly  into  the  sterile  test-tube  without  fear  of  con- 
tamination.    If,  after  the  puncture  has  been  made, 
the  fluid  does  not  flow  into  the  test-tube,  the  holder 
is  removed   and  a  stilette   passed  down   the  needle. 
Before  adjusting  the  needle  to  the  holder,  the  needle 
should   be  dipped   into  a  test-tube  containing  auto- 
claved  olive  oil.     When  making  the  lumbar  puncture, 
the  spine  should  be  flexed  so  as  to  open  out  the  inter- 
laminal  spaces  as  much  as  possible.     If  the  patient  is 
able  to  sit  up,  lumbar  puncture  is  most  easily  and 
conveniently  performed  if  the  patient  sits  on  a  stool 
with  his  back  bent  well  forward,  his  knees  separated, 
and  hands  touching  the  ground.     If,  however,  he  is 
unable  to  leave  the  bed,  he  should  be  placed  on  his 
side,    with    his   knees    and   shoulders   brought   close 
together.     When   making   the  puncture,    the   needle 
passes  easily  in  for  about   ij  to  2  inches,  when  it 
will  meet  the  interlaminal  ligament,  through  which 
it  must  be  firmly  pushed  into  the  cerebro-spinal  canal, 
when  the  fluid  escapes  into  the  tube.     Occasionally 
the  needle  becomes  blocked  in  its  passage  through 
the    tissues,    and    no    cerebro-spinal    fluid    escapes, 
although  the  point  is  in  the  cerebro-spinal  fluid.    The 
tube  should  be  removed  before  the  needle  is  with- 
drawn, as  during   the   withdrawal  some  blood  may 
escape  into  the  needle  and  contaminate  the  fluid.     It 
is  obvious  that   no   correct  leucocyte  count  can   be 
made  if  there  is  any  blood  present.     It  is  therefore 
wisest  to  allow  a  few  c.c.  of  cerebro-spinal  fluid  to 
escape  into  the  first  test-tube,  and  then,  removing  this 
tube,  to  replace  it  by  a  second.     Any  trace  of  blood 


CEREBROSPINAL  FLUID  99 

will  be  washed  away  by  the  passage  of  the  first 
sample,  and  the  second  sample  will  be  uncontamin- 
ated.  The  second  tube  is  now  removed,  and  kept  for 
cytological  examination.  The  first  tube  is  used  again 
during  the  withdrawal  of  the  needle. 

CYTOLOGICAL  EXAMINATION 

Lymphocytosis  of  the  cerebro-spinal  fluid  occurs 
in  tabes  and  general  paralysis,  which,  according  to 
Mott,  is  not  diminished  with  antisyphilitic  treatment. 
Plant,  however,  has  recorded  a  distinct  sinking  in 
the  cellular  contents  (424  to  120  cells  per  c.mm.)  in 
a  case  of  cerebral  syphilis,  without  any  change  in  the 
Wassermann  reaction. 

Lymphocytosis  also  occurs  to  a  marked  degree  in 
sleeping-sickness,  and  has  been  found  in  Landry's 
paralysis  and  in  the  subacute  combined  degeneration 
of  pernicious  anaemia,  and,  according  to  Sicard,  in 
herpes  zoster.  Lymphocytosis,  however,  cannot  be 
regarded  as  absolutely  diagnostic  of  meningitis  ;  but 
Mott  considers  it  strong  presumptive  evidence,  and, 
when  combined  with  other  facts,  he  considers  the 
existence  of  a  lymphocytosis  of  the  cerebro-spinal 
fluid  as  a  valuable  sign  of  syphilitic  or  para- 
syphilitic  affections  of  the  central  nervous  system 
or  meninges. 

Normal  cerebro-spinal  fluid  contains  no  poly- 
morphonuclears, and  very  few,  if  any,  lymphocytes. 
The  lymphocytosis  of  tabes  and  general  paralysis  is, 
according  to  Purves  Stewart,  more  marked  than  in  any 
other  form  of  organic  disease.     In  acute  inflammatory 


loo  SYPHILIS  AND  PARASYPHILIS 

processes  there  is  a  polymorphonuclear  leucocytosis, 
and  in  chronic  inflammatory  processes  a  lymphocytosis. 
In  acute  tubercular  meningitis  both  polymorpho- 
nuclears and  lymphocytes  may  be  present  in  large 
numbers,  the  majority  of  cells  present  being  lympho- 
cytes, though  as  many  as  30  per  cent,  of  polymorpho- 
nuclears are  sometimes  present. 

Plant  considers  that  a  cytological  examination  is 
normal  if  less  than  six  leucocytes  are  found  per  c.mm. 
If  ten  or  more  cells  are  present,  the  fluid  must  be 
considered  pathological.  Countings  from  six  to  ten  he 
considers  doubtful.  Out  of  fifty-six  cerebro-spinal 
fluids  obtained  from  cases  that  were  definitely  non- 
syphilitic,  in  forty-eight  cases  the  cell-findings  were 
entirely  negative,  and  there  were  under  six  cells  in 
each  c.mm.  In  four  cases  normal  findings  were 
increased,  but  not  above  the  number  which  was  to 
be  regarded  as  pathological  (ten  cells  to  i  c.mm.). 
In  the  remaining  four  cases,  however,  there  was  found 
a  pathological  cell  increase,  while  both  the  spinal 
fluid  and  blood-serum  gave  completely  negative 
Wassermann  reactions. 

Out  of  ten  cases  of  syphilis  with  secondary  symptoms 
that  were  examined,  three  showed  a  positive  cyto- 
logical count ;  while  of  nine  cases  of  latent  tertiary 
syphilis  showing  a  positive  Wassermann  reaction  in 
the  blood,  two  showed  a  positive  cytological  count  of 
the  cerebro-spinal  fluid. 

Ravaut  found  a  marked  lymphocytosis  of  the 
cerebro-spinal  fluid  during  the  secondary  stage  of 
syphilitic  infection  which  ran  pari  passii  with  the 
cutaneous  eruption.     In  a  case  of  extensive  papula,r 


CEREBROSPINAL  FLUID  loi 

syphilis  he  found  the  cerebro-spinal  fluid  quite  turbid 
with  lymphocytes.  The  lymphocytosis  was  not  seen 
in  tertiary  syphilis  unless  the  eye  or  central  nervous 
system  were  affected. 

Plant  comes  to  the  conclusion  that  the  phenomenon 
of  lymphocytosis  does  not  go  parallel  with  the 
Wassermann  reaction  of  the  spinal  fluid,  and  that 
the  mechanism  which  produces  the  lymphocytosis  is 
not  identical  with  that  which  causes  the  appearance 
of  a  complement-fixing  substance  in  the  cerebro- 
spinal fluid.  He  also  considers  that  the  appearance 
of  the  Wassermann  reaction  in  the  blood  need  not  be 
accompanied  by  an  increase  of  the  lymphocytes  in  the 
spinal  fluid,  and  that  there  may  be  a  cellular  increase 
in  the  cerebro-spinal  fluid  in  the  latent  tertiary  stages 
without  any  syphilitic  manifestations  in  the  central 
nervous  system. 

There  appears  to  be  no  parallellism  between  the 
results  obtained  by  a  cytological  examination  of  the 
cerebro-spinal  fluid  and  the  Wassermann  reaction. 
There  may  be  a  distinct  lymphocytosis  without  any 
power  whatever  of  complement-fixing. 

The  cell-count  should  be  made  shortly  after  the 
withdrawal  of  the  fluid,  and  the  author  thinks  Fuch's 
and  Rosenthal's  counting  chamber  the  most  con- 
venient for  the  absolute  leucocyte  count.  This 
chamber  has  a  depth  of  0*2  mm.,  and  since  its  ruled 
floor  occupies  an  area  of  16  mm.  square,  the  entire 
column  which  comes  under  the  operation  of  counting 
measures  3*2  mm.  The  fluid  is  mixed  in  a  mixing 
pipette  whose  bulb  has  a  capacity  which  is  ten  times 
greater    than    that    of    the    capillary    portion.      The 


I02  SYPHILIS  AND  PARASYPHILIS 

diluent  is  a  stainiog  solution  of  the  following  com- 
position : 

Methyl  violet         ...  ...       o*io  parts. 

Distilled  water      ..,  ...     50         ,, 

Glacial  acetic  acid  ...       2  ,, 

With  this  medium  the  cerebro-spinal  fluid  is  mixed  in 
the  proportion  of  i  of  stain  to  g  of  cerebro-spinal  fluid. 
To  prepare  the  diluted  mixture,  obtain  a  sample  of 
the  cerebro-spinal  fluid  immediately  after  puncture, 
and,  after  repeatedly  shaking  it  up  lightly,  transfer  a 
small  quantity  to  a  dish,  aspirate  some  of  the  stain 
with  the  pipette  up  to  the  gauge-mark  i,  and  then 
draw  up  a  sufficient  quantity  of  the  cerebro-spinal 
fluid  until  the  bulb  is  filled  up  to  the  gauge-mark  11. 
Close  the  point  of  the  pipette  with  the  tip  of  the 
finger,  and  shake  the  fluid  in  the  bulb  well  for  some 
time.  Having  insured  a  good  mixture,  expel  the  fluid 
contained  in  the  capillary  stem,  and  then  transfer  a 
drop  of  the  mixture  to  the  counting  chamber.  The 
floor  of  the  chamber  should  be  counted  right  through, 
since  the  cerebro-spinal  fluid  contains  a  relatively 
small  number  of  cells.  The  average  number  of  cells 
contained  in  a  cubic  millimetre  of  the  cerebro-spinal 
fluid  is  accordingly  : 

10  X  ^       lOZ  1      z 

x=^ =  -—--,  or  very  nearly  -, 

3*2  X  9     28-8  3 

where  z  is  the  total  number  of  cells  counted  over  the 
entire  floor  of  the  chamber. 

Should  the  total  number  of  cells  covering  the  floor 
of  the  chamber  happen  to  be  excessively  small,  the 
latter  should  be  charged  once  more  and  a  fresh  count 
made. 


CEREBROSPINAL  FLUID  103 

A  differential  leucocyte  count  should  also  be  made, 
and  for  this  purpose  the  cerebro-spinal  fluid  is  centri- 
fugalized  in  a  conical  glass  tube,  and  a  film  made  of 
the  deposit  at  the  tapered  end  of  the  tube.  This  film 
should  be  stained  with  Jenner's  stain. 

Of  21  normal  cases  of  cerebral  syphilis  examined 
by  Plaut,  only  i  was  cytologically  negative  ;  3  were 
on  the  border-line  (5  to  9  cells  per  i  c.mm.),  and  17 
showed  a  distinct  cellular  increase,  the  highest  count 
showing  424  cells. 

Leucocytosis  is  absent  in  functional  neurosis. 

Ravaut  has  shown  that  in  acute  and  chronic 
meningitis  the  cellular  element  and  spinal  fluid  are 
proportional  to  the  degree  and  intensity  of  the  inflam- 
mation. He  considers  the  presence  of  lymphocytosis 
as  an  indication  for  energetic  antisyphilitic  treatment. 
He  considers  the  degree  of  lymphocytosis  greater  in 
early  than  late  cases  ;  and  in  old  syphilitics,  other 
than  parasyphilitics  with  no  manifestations,  the 
cerebro-spinal  fluid  is  normal. 

Babinski  and  Naglotti  have  said  that  lymphocytosis 
may  precede  the  appearance  of  the  Argyll- Robinson 
pupil  in  tabes. 

Funhe  considers  that  lymphocytosis  is  not  charac- 
teristic of  syphilitic  nervous  diseases,  and  that  it  is 
only  present  if  the  meninges  are  involved. 

From  the  above  it  will  be  seen  that  most  authorities 
agree  that  a  negative  cytological  examination — namely, 
the  presence  of  less  than  six  cells  per  c.mm. — will 
exclude  general  paralysis,  syphilitic  meningitis,  and 
tabes.  In  syphilitic  or  parasyphilitic  affections  par- 
ticularly no  polymorphonuclear  cells  are  seen  ;  whereas 


I04  SYPHILIS  AND  PARASYPHILIS 

in  chronic  tubercular  meningitis,  although  in  later 
stages  there  may  be  as  many  as  10,000  lymphocytes 
per  c.mm.,  there  are  usually  also  a  considerable 
number  of  polymorphonuclear  cells,  which  will  prob- 
ably|form  25  per  cent,  of  the  total  leucocyte  count. 

With  acute  meningeal  diseases,  such  as  acute 
syphilitic  meningitis,  acute  cerebro-spinal  meningitis 
(or  acute  tuberculous  meningitis),  the  cellular  increase 
is  chiefly  polymorphonuclear. 

WASSERMANN  REACTION 

Of  9  cases  of  active  secondary  syphilis  examined 
by  Plant,  the  cerebro-spinal  fluid  was  negative  in  all, 
as  it  also  was  in  4  cases  examined  in  the  secondary 
latent  stage. 

Of  II  cerebro-spinal  fluids  taken  from  patients  in 
the  latent  tertiary  stage,  all  were  negative. 

Of  154  cases  of  general  paralysis,  146  were  posi- 
tive, 6  negative,  and  2  doubtful ;  while  of  20  cases 
of  cerebral  syphilis,  17  were  negative,  and  only 
3  positive. 

General  paralysis  is  the  only  syphilitic  or  para- 
syphilic  afl"ection  in  which  a  negative  result  is  of  any 
very  great  value  ;  but  here  it  is  of  very  great  value 
indeed,  and  a  negative  Wassermann  reaction  in  the 
blood  or  cerebro-spinal  fluid  will  practically  exclude 
this  condition. 

A  positive  Wassermann  reaction  of  the  cerebro- 
spinal fluid  indicates  that  the  patient  either  has  general 
paralysis,  tabes,  or  cerebral  syphilis. 

Plant  has  obtained  a  positive  Wassermann  reaction 
in  the  blood-serum  in  every  case  in  which  a  positive 


CEREBROSPINAL  FLUID  105 

reaction  was  recorded  in  the  cerebro-spinal  fluid  ;  but 
other  observers,  including  the  author,  have  very  occa- 
sionally met  a  cerebro-spinal  fluid  that  was  positive  in 
which  the  blood-serum  was  negative. 

In  cases  in  which  the  question  for  diagnosis  is  the 
presence  or  absence  of  general  paralysis,  Plant  recom- 
mends that  the  blood  should  be  first  examined.  If 
there  is  a  positive  result,  lumbar  puncture  is  then 
performed ;  but  if  the  blood  reaction  is  negative, 
lumbar  puncture  is  considered  contra-indicated,  as 
the  case  can  be  considered  almost  certainly  not  one 
of  general  paralysis ;  whereas  a  positive  reaction  in 
the  serum  alone  indicates  absolutely  nothing  concern- 
ing general  paralysis,  and  only  shows  that  the  patient 
has  syphilis. 

A  positive  Wassermann  reaction  in  the  cerebro- 
spinal fluid  does  not  appear  to  be  influenced  by 
antisyphilitic  treatment.  This  may  possibly  be  due 
to  the  drugs  used  failing  to  reach  the  cerebro-spinal 
fluid. 

It  has  been  found  in  certain  cases  of  trypanosomiasis 
that  some  arsenical  preparations  are  able  to  remove 
the  trypanosomes  from  the  blood,  but  not  from  the 
cerebro-spinal  fluid  ;  and  it  has  also  been  recorded 
that  potassium  iodide,  though  present  in  the  blood, 
cannot  be  found  in  the  cerebro-spinal  fluid. 

This  isolation  of  the  cerebro-spinal  fluid  may  also 
account  for  the  difficulty  in  influencing  parasyphilitic 
aff"ections  by  means  of  drugs  administered  either 
intravenously,  intramuscularly,  or  by  the  mouth,  and 
possibly  there  may  be  a  future  for  treatment  directly 
applied  to  the  cerebro-spinal  fluid.   Success  has  already 


io6  SYPHILIS  AND  PARASYPHILIS 

been  reported  by  Macintosh,  Martin,  Flexner,  and 
Knolle  in  the  treatment  of  cerebro-spinal  fever  by 
means  of  intraspinal  injections  of  serum  containing 
antibody. 

Schmorl  is  of  the  opinion,  also,  that  the  cerebro- 
spinal fluid  is  cut  off  from  the  intraventricular  fluid, 
and  finds  that  in  cases  of  marked  jaundice  the  intra- 
ventricular fluid  contains  no  trace  of  bile  pigment, 
although  the  pigment  may  be  present  in  the  cerebro- 
spinal fluid.  He  also  reports  that  in  one  case  of 
diabetes,  though  a  reducing  substance  was  found  in 
considerable  quantity  in  the  spinal  fluid,  yet  none  was 
found  in  the  intraventricular  fluid.  The  cerebro-spinal 
fluid  was  examined  for  the  Wassermann  reaction  in 
seven  cases  of  general  paralysis  ;  in  all  cases  the 
Wassermann  reaction  of  the  blood  and  cerebro-spinal 
fluid  was  positive,  whereas  in  only  one  was  the  re- 
action of  the  intraventricular  fluid  positive.  Schmorl 
therefore  considers  that  the  intraventricular  cavities 
are  closed  off  from  the  subarachnoid  space. 

In  the  cases  in  which  the  intraventricular  fluid 
contained  bile  pigment  or  gave  a  positive  Wassermann 
reaction,  Schmorl  found  that  the  epithelium  of  the 
choroid  plexus  was  degenerate ;  whereas  in  those 
cases  in  which  the  fluid  was  free  from  pigment,  or 
the  Wassermann  reaction  negative,  the  epithelium  of 
the  choroid  plexus  was  intact. 

Browning  and  Mackenzie  made  a  similar  examina- 
tion in  four  cases  of  general  paralysis.  The  cerebro- 
spinal fluid  was  positive  in  every  case,  whereas  in 
only  two  did  the  intraventricular  fluid  give  a  positive 
reaction.     They  also  found  that  both  the  cases  which 


CEREBROSPINAL  FLUID  107 

gave  a  positive  reaction  showed  a  degenerative  con- 
dition of  the  choroid  plexus,  whereas  in  the  negative 
cases  these  degenerative  changes  were  not  observed. 

Mott  has  also  found  that,  though  reactions  which  at 
first  are  negative  may  later  become  positive,  no  patient 
suffering  from  general  paralysis,  whose  cerebro-spinal 
fluid  has  once  given  a  positive  reaction,  has  ever 
given  a  negative  reaction  at  any  subsequent  examina- 
tion. He  considers  that  antibodies  accumulate  in  the 
cerebro-spinal  fluid  in  proportion  as  the  process  of 
decay  of  the  neurones  proceeds,  and  he  thinks  that 
there  is  a  parallelism  between  the  amount  of  decay  of 
the  brain  and  the  degree  of  the  positive  character  of 
the  reaction. 

Marie  and  Levaditi  have  also  found  that  there  is 
a  parallelism  between  the  rapidity  of  the  progress  of 
general  paralysis  and  the  degree  and  intensity  of  the 
Wassermann  reaction. 

Mott  considers  that  the  Wassermann  reaction  gives 
a  valuable  means  of  diagnosis,  which  is  especially 
useful  when  applied  to  the  cerebro-spinal  fluid  to 
determine  the  presence  or  absence  of  general  paralysis. 
He  considers  that  the  amount  of  complement-fixing 
substance  is  in  proportion  to  the  activity  and  length 
of  duration  of  the  diseases,  and  that  these  substances 
are  lipoids  and  globulins,  which  are  of  tissue  origin, 
and  arise  from  tissue  destruction  caused  by  the  present 
or  past  action  of  the  syphilitic  virus. 

Nonne  has  pointed  out  that,  when  making  the 
Wassermann  test  with  cerebro-spinal  fluid,  consider- 
ably more  of  the  test-fluid  should  be  used  in  the  case 
of  cerebro-spinal   fluid   compared   with    serum.     He 


io8  SYPHILIS  AND  PARASYPHILIS 

states  that  i  c.c.  can  be  employed  in  the  original 
technique  without  fear  of  the  positive  reaction  in 
non-syphilitic  cases. 

Candler  is  also  of  the  opinion  that  a  positive 
reaction  may  be  missed  unless  considerable  quantities 
of  the  cerebro-spinal  fluid  are  used,  and  instances  a 
case  in  which  complete  complement-fixation  occurred 
when  0-8  c.c.  of  fluid  was  used,  although  there  was 
complete  haemolysis  with  0*5  c.c. 

As  the  cerebro-spinal  fluid  contains  no  complement, 
it  is  unnecessary  to  heat  it. 

CHEMICAL  EXAMINATION 

The  increase  in  proteid-content  can  usually  be 
demonstrated  in  general  paralysis  and  tabes,  especi- 
ally in  the  former. 

Globulin  Reacton  :  Nonne  and  Afelt. — The  fluid  is 
mixed  with  an  equal  quantity  of  saturated  ammonium 
sulphate.  If  turbidity  appears  in  three  minutes,  the 
reaction  is  positive. 

Marie  also  considers  that  there  is  a  marked 
parallelism  between  the  Wassermann  reaction  of  the 
cerebro-spinal  fluid  and  the  albumin  reaction,  for 
which  he  uses  equal  quantities  of  centrifugalized 
cerebro-spinal  fluid  and  saturated  ammonium  sulphate 
solution.  He  regards  the  reaction  as  positive  when 
boiling  produces  a  turbidity. 

Noguchi's  Method. — One  or  two  parts  of  spinal 
fluid  are  mixed  with  five  parts  of  a  10  per  cent,  dilution 
of  butyric  acid  in  physiological  salt  solution,  and  the 
mixture  is  boiled   for  a   few  seconds.     One  part  of 


CEREBROSPINAL  FLUID  109 

normal  NaOH  solution  is  added  quickly  to  the  heated 
mixture,  and  the  whole  is  again  boiled  for  a  few 
seconds.     The  actual  quantities  recommended  are  : 

Cerebro-spinal  fluid    ...  ...     o*i  c.c.  or  0*2  c.c. 

Butyric  acid  solution  ...  ...     0*5  c.c. 

Normal  sodium  hydrate  solution     o-i  c.c. 

The  rapidity  with  which  the  precipitation  falls  is 
proportional  to  the  amount  of  proteid  present,  and 
Noguchi  considers  that  a  positive  result  has  been 
obtained  when  the  precipitate  settles  within  two 
hours. 

On  adding  fresh  Fehling's  solution  and  boiling, 
a  reducing  body  (?  dextrose)  is  found  in  normal 
cerebro-spinal  fluids,  which  is  reduced  in  amount  or 
may  be  absent  if  meningitis  is  present. 


CHAPTER  X 
URINE 

A  CONSIDERABLE  percentage  of  syphilitics  show 
evidence  of  nephritis  in  their  urine.  It  is,  however, 
difficult  to  say  to  what  degree  this  nephritis  is  primarily 
syphilitic  or  only  the  ordinary  forms  occurring  in 
syphilitic  subjects. 

Speiss  has  reported  that  of  220  syphilitic  patients 
examined  post-mortem,  the  kidneys  were  affected  in 
131,  grouped  under  the  following  heads  : 

Amyloid  degeneration          ...  ...  ...  42 

Parenchymatous  nephritis  ...  ...  ...  21 

Sclerosis  ...             ...             ...  ...  ...  18 

Interstitial  nephritis             ...  ...  ...  16 

Atrophy   ...             ...             ...  ...  ..,  11 

Sclero-gummatous  nephritis  ...  ...  7 

Various  inflammations  only  partly  attributable 

to  syphilis       ...             ...  ...  ...  16 

Petersen  considers  that  the  kidneys  are  affected  in 
3  per  cent,  of  cases  in  secondary  syphilis. 

The  onset  of  secondary  symptoms  is  frequently 
accompanied  by  albuminuria  which,  however,  may  be 
slight  and  transient,  and  of  the  same  nature  as  the 
albuminuria  accompanying  any  other  acute  infection 
which  cannot  be  considered  a  definite  nephritis. 

Acute  nephritis  arises  during  the  secondary  stage 

no 


URINE  III 

and  generally  within  the  first  year,  or  at   least  two 
years  from  infection. 

Many  cases  of  syphilitic  nephritis  present  an  extra- 
ordinarily intense  albuminaria  with  few  other  signs. 
The  urine  becomes  solid  on  boiling,  and  the  conditions 
may  be  present  for  weeks  without  any  other  marked 
signs  of  illness.  Notwithstanding  the  large  quantity 
of  albumin  there  may  be  very  little  sediment  and  few 
casts,  leucocytes,  or  red  blood-cells. 

In  subacute  syphilitic  nephritis  the  urine  is  di- 
minished in  quantity,  when  at  the  height  of  the  disease 
it  varies  from  200  to  250  c.c,  and  as  the  case  improves 
it  increases,  and,  if  the  patient  be  encouraged  to  drink, 
may  reach  5  to  6  litres.  Its  specific  gravity  is  normal 
or  slightly  increased,  in  some  cases  up  to  1040.  The 
albumin  is  present  in  quantities  of  about  0*4  to  o"8  per 
cent.  The  specific  gravity  varies  inversely  with  the 
quantity.  The  reaction  is  faintly  acid,  but  in  some 
cases  alkaline,  even  when  fresh,  and  in  all  cases 
quickly  becomes  alkaline.  It  is  usually  cloudy  from 
the  large  amount  of  sediment,  and  foaming  easily  on 
shaking,  because  of  the  amount  of  albumin  which  is 
present.  It  seldom  reaches  i  per  cent.,  though  for 
months  it  may  vary  from  0*4  to  o-8.  The  urine  is 
somewhat  diminished.  Red  blood-cells  are  practically 
always  found,  and  coarsely  granular,  fatty,  and  waxy 
casts. 

Several  writers  state  that  they  have  found  the 
Spivochcdta  pallida  in  the  urine  of  patients  suffering  with 
florid  secondary  syphilis,  but  the  majority  of  observers 
have  failed  to  detect  the  organism  in  urine. 

In  chronic  intestitial  nephritis  the  urine  is  usually 


112  SYPHILIS  AND  PARASYPHILIS 

increased  in  quantity.  The  specific  gravity  is  usually 
lower  than  normal — 1005  ^'^  loio  ;  this  is  especially 
noticeable  in  the  morning.  There  is  usually  only  a 
trace  of  albumin,  which  is  seldom  present  in  greater 
quantities  than  0*05  per  cent.  A  few  hyaline  casts, 
red  blood-cells,  and  epithelial  cells  are  usually  found. 

Lardaceous  (amyloid)  disease  of  the  kidney 
may  be  superimposed  on  any  form  of  nephritis. 

Traube's  classical  description  of  urine  in  lardaceous 
disease  of  the  kidney  is  that  '  it  is  increased  in  amount, 
pale,  clear,  faintly  acid,  of  low  specific  gravity  (1002- 
1005)  and  that  it  contains  abundant  albumin  and  very 
few  casts.'  Albumin,  however,  may  not  be  found  at 
all,  or  only  in  traces,  and  casts  may  be  numerous  when 
they  are  usually  fatty  or  hyaline.  Epithelial  cells  and 
red  blood-discs  are  rarely  seen. 


CHAPTER  XI 

CLINICAL  VALUE  OF  THE  WASSER- 
MANN  REACTION 

LATENT   SYPHILIS 

In  the  old  days  the  only  method  of  diagnosing  the 
presence  of  syphilitic  infection  was  by  clinical  symp- 
toms, and  it  was  extremely  difficult  to  give  an  opinion 
as  to  when  the  patient  was  cured  or  for  how  long 
treatment  should  be  continued,  as  frequently,  after  the 
patient  had  been  six  months  under  treatment,  all 
symptoms  would  disappear.  At  first,  a  year's  treat- 
ment was  considered  sufficient.  This  period  was 
gradually  lengthened  to  two  and  three  years,  and 
recently  five  years'  treatment  has  been  considered 
necessary  by  some  authorities,  with  occasional  courses 
prolonged  indefinitely  afterwards. 

It  is  generally  accepted  now  that  a  positive  Wasser- 
mann  reaction  is  sufficient  evidence  of  active  infection 
to  justify  a  continuation  of  treatment,  even  when  no 
other  symptoms  are  present. 

In  syphilis  which  has  been  treated  there  is  always 
a  tendency  for  the  symptoms  to  disappear  spontane- 
ously, only  to  recrudesce  later.  Browning  and  Mac- 
kenzie   describe    this    latent   period   as    '  a    state   of 

113  8 


ti4  SYPHILIS  AND  PARASYPHILIS 

equilibrium  between  the  host  and  the  parasite,'  and 
Ehrlich  has  given  it  the  name  of  '  non-sterilizing 
immunity.'  During  this  latent  period  about  50  per 
cent,  of  cases  still  give  a  positive  Wassermann  reaction, 
which  enables  the  infection  to  be  diagnosed  so  that 
the  patient  may  be  placed  on  appropriate  treatment, 
and  the  recrudescence  of  the  infection  and  the  conse- 
quent formation  of  lesions  prevented. 

In  some  cases  in  which  the  blood  is  examined 
during  the  latent  period,  the  Wassermann  reaction  is 
found  to  be  negative,  but  if  antisyphilitic  treatment  is 
given  the  reaction  becomes  positive.  Similarly,  occa- 
sionally the  symptoms  are  aggravated  for  a  short  time 
when  the  patient  is  put  under  treatment.  This  lighting 
up  of  the  disease,  as  evidenced  by  the  appearance  of  a 
positive  Wassermann  in  a  blood  which  before  was 
negative,  or  by  an  increase  in  the  manifestations  of 
the  disease,  has  been  given  the  name  of  the  *  Jarisch- 
Herxheimer  reaction.'  It  is  supposed  to  be  caused 
by  the  setting  free  of  the  endotoxins  contained  in  the 
bodies  of  the  spirochaetes  which  have  been  destroyed 
as  the  result  of  the  treatment.  Another  theory 
advanced  is  that  the  reaction  is  produced  by  the 
stimulation  of  the  spirochaetes  by  a  dose  of  a  drug 
which  has  been  insufficient  to  kill  them.  The  author 
is  of  the  opinion  that  the  former  rather  than  the  latter 
theory  is  the  correct  one. 

A  positive  Wassermann  reaction  must  be  regarded 
as  resulting  from  some  alteration  or  destruction  of 
tissue,  caused  by  a  toxin  produced  by  the  spirochaetes. 
It  therefore  takes  a  little  time  for  a  positive  reaction 
to  develop,  and  the  reaction  is  not  due  simply  to  the 


CLINICAL  VALUE  OP  REACTION  115 

presence  of  the  spirochaetes  themselves.  Bruck  has 
shown  that  the  serum  of  monkeys  becomes  positive 
about  the  same  time  as  the  organs  become  infective, 
as  shown  by  inoculation  experiments,  and  Levaditi 
and  Yamanouchi  consider  that  the  time  when  the  skin 
becomes  immune  to  further  inoculations  and  the  time 
.when  the  Wassermann  reaction  becomes  positive, 
synchronize. 

FOR  DIFFERENTIAL  DIAGNOSIS 

That  the  Wassermann  reaction  is  of  the  greatest 
possible  value  for  diagnosis  has  been  proved  beyond 
question,  and  the  physician,  surgeon,  gynaecologist, 
ophthalmic  surgeon,  lary  ngologist,  aurist,  dermatologist, 
and  the  neurologist^  are  all  equally  aided  in  diagnosis 
by  this  reaction. 

Medicine. — The  syphilitic  fever,  which  sometimes 
accompanies  either  the  primary,  secondary,  or  tertiary 
lesions,  may  be  accompanied  by  anaemia,  loss  of  weight, 
pain  or  swelling  of  joints,  and  may  be  mistaken  for 
rheumatic  fever,  phthisis,  malaria,  or  enteric  fever. 

Pulmonary  syphilis,  though  extremely  rare,  when 
present  may  be  exceedingly  difficult  to  diagnose  from 
phthisis,  and,  in  the  absence  of  the  tubercle  bacilli 
from  the  sputum,  the  Wassermann  reaction  is  the 
most  important  guide  to  a  correct  diagnosis. 

In  syphilis  of  the  heart,  producing  symptoms  of 
heart  failure  or  anginal  attacks,  the  syphilitic  origin 
of  the  disease  is  often  missed,  and  Osier  considers 
that  the  presence  of  heart  failure  in  a  young  or  middle- 
aged  person  in  whom  there  is  no  history  of  rheumatic 


li6  SYPHILIS  AND  PARASYPHILIS 

fever  should  always  arouse  a  suspicion  of  syphilis. 
It  has  long  been  suspected  that  the  majority  of  cases 
of  aortic  aneurism  and  aortitis  were  syphilitic  in 
origin.  This  has  been  proved  to  be  the  case  by  the 
Wassermann  reaction,  practically  every  case  of  aortic 
aneurism  giving  a  positive  result.  In  the  absence  of 
antisyphilitic  treatment,  therefore,  a  negative  Wasser- 
mann almost  excludes  aortic  aneurism. 

A  certain  proportion  of  cases  of  gastric  ulcer  are 
considered  by  some  observers  to  be  syphilitic  in  origin. 

The  liver  is  frequently  attacked  in  syphilis.  Osier 
and  Gibson  consider  that  in  about  5  per  cent,  of  cases 
of  tertiary  syphilis,  exclusive  of  amyloid  diseases, 
symptoms  are  referable  to  diseases  of  the  liver. 

As  we  have  seen  in  the  last  chapter,  syphilis  may 
frequently  be  the  cause  of  renal  diseases. 

Surgery. — The  value  of  the  Wassermann  reaction 
for  the  differential  diagnosis  of  malignant  disease  or 
tubercular  disease  from  syphilis  is  obvious. 

There  is  hardly  any  tumour  of  the  bone  or  skin,  or 
any  form  of  chronic  ulceration,  in  which  operative 
procedure  should  be  undertaken,  without  first  testing 
the  Wassermann  reaction,  and,  if  positive,  giving  the 
patient  some  antisyphilitic  remedy  with  a  view  to 
finding  out  whether  the  lesion  in  question  is  syphilitic 
or  not. 

Syphilitic  adenitis,  especially  that  occurring  in  the 
tertiary  stage,  has  been  erroneously  diagnosed  as 
Hodgkin's  disease. 

Obstetrics  and  Gynaecology. — Dr.  Franz  Weber 
has  shown  that  some  cases  of  endometritis  and  of  per- 
sistent menorrhagia  may  depend  on  a  latent  sjj^philitic 


CLINICAL  VALUE  OF  REACTION  117 

affection,  the  recognition  of  which  by  the  Wassermann 
reaction  may  indicate  the  line  of  successful  treatment. 

Weber  determined  the  Wassermann  reaction  in  67 
cases  of  pregnancy  which  terminated  before  the  twenty- 
eighth  week,  and  found  that  of  35  ending  within  the 
first  sixteen  weeks,  not  one  gave  a  positive  result. 
On  the  other  hand,  of  the  32  later  cases,  12  without 
any  ascertained  history  or  clinical  evidence  of  syphilis 
gave  a  positive  reaction,  and  in  the  examination  of 
9  dead  foetuses  from  these  12  cases  spirochaetes  were 
found  in  the  organs  of  6.  Among  33  cases  of  recurrent 
abortion,  6  only  gave  a  positive  reaction.  The  ex- 
amination of  the  macerated  foetus  show  that  in  84  per 
cent,  the  organs  contain  spirochaetes,  which  were  found 
in  the  largest  number  in  the  adrenal  capsules. 

Ophthalmology. — Chancre,  gummata,  and  tertiary 
syphilitic  ulcers  occasionally  occur  on  the  eyelids,  and 
keratitis,  iritis,  retinitis,  choroido  retinitis,  and  optic 
neuritis  may  all  be  syphilitic  in  origin. 

Nervous  Diseases. — The  value  of  the  Wasser- 
mann reaction  in  nervous  diseases  is  discussed  in  the 
next  chapter. 

Although,  in  the  absence  of  a  few  diseases,  a  positive 
reaction  can  be  taken  as  pathognomic  of  syphilis,  it 
must  always  be  remembered  that  a  negative  reaction 
does  not  necessarily  put  syphilis  out  of  court,  especially 
in  cases  in  which  obvious  lesions  are  absent.  In  the 
secondary  and  tertiary  stages  from  10  to  20  per  cent, 
of  cases  fail  to  give  a  positive  reaction,  and  in  latent 
cases  and  cases  in  which  there  are  no  symptoms 
50  per  cent,  of  cases  are  negative.  A  succession  of 
negative  reactions  must  be  obtained  before  syphilis 


ii8  SYPHILIS  AND  PARASYPHILIS 

can  be  excluded,  and  even  then  the  exclusion  would 
not  be  absolute,  but  only  probable. 

FOR  CONTROLLING  TREATMENT 

Neisser  is  firmly  convinced  that  a  positive  reaction 
is  a  sure  symptom  of  disease  and  an  indication  of  the 
continued  presence  of  spirochaetes  in  the  infected  body, 
and  that  consequently  in  all  cases  which  give  a  certain 
positive  reaction  a  recurrence  is  possible,  and  that  all 
such  cases  should  be  put  under  treatment. 

The  Wassermann  reaction,  therefore,  furnishes 
grounds  for  the  treatment  of  those  patients  whom 
we  previously  did  not  treat  because  the  affection  was 
not  recognized,  and  of  those  whom  we  had  ceased  to 
treat  because  we  believed  them  to  be  cured. 

Neisser  considers  that  the  serum  diagnosis  is  indis- 
pensable before  giving  an  opinion  on  any  syphilitic 
cases  which  presents  no  manifest  symptoms  of  syphilis, 
and  he  considers  that  the  Wassermann  reaction  alone 
can  help  us  to  decide  the  difficult  question  as  to  how 
long  treatment  must  be  continued. 

In  the  Cavendish  Lecture  in  191 1,  Neisser  said  : 

'  I  cannot  understand  how  in  the  present  day  medical 
men  fail  to  make  use  of  this  excellent  aid  to  the  diag- 
nosis of  syphilis.  One  must  urgently  demand  that 
every  individual,  of  whom  even  the  slightest  suspicion 
is  entertained  that  any  disease  may  be  produced  by  a 
known  or  unknown  syphilitic  infection,  must  have  his 
serum  examined  so  as  to  disclose  these  hidden  or 
latent  cases,  and  in  this  way  to  cure  them  and  to 
protect  them  against  the  much-dreaded  parasyphilitic 
complication.' 


CLINICAL   VALUE  OF  REACTION  119 

A  single  negative  reaction  obtained  with  the  serum 
of  a  patient  undergoing  treatment  by  mercury  or 
salvarsan  means  Httle  but  that  the  patient  is  reacting 
to  such  treatment.  A  series  of  negative  results  taken 
at  intervals  of  three  to  six  months  after  all  treatment 
has  been  given  up  is  necessary  before  the  patient  can 
be  regarded  as  cured,  and  even  then,  until  twenty 
years  have  passed,  we  cannot  be  absolutely  certain 
that  the  disease  is  completely  and  permanently  obliter- 
ated and  that  no  late  manifestations  will  ever  occur. 
It  is  most  important  to  remember  that  about  10  per 
cent,  of  untreated  cases  of  syphilis  fail  to  give  a 
positive  reaction  at  the  first  examination,  and  that 
therefore  a  negative  reaction  only  gives  a  90  per  cent, 
probability  of  freedom  from  infection. 

If  in  recently  acquired  syphilis  after  several  months' 
treatment  the  reaction  continues  to  be  strongly  positive, 
and  large  doses  of  complement  are  still  fixed,  this  is 
an  indication  that  the  treatment  is  inefficient,  and 
that  more  rigorous  methods  should  be  adopted.  If, 
however,  after  each  course  of  treatment  a  smaller 
amount  of  complement  is  fixed,  or  the  intervals  before 
a  positive  reaction  returns  become  longer  and  longer, 
we  may  conclude  that  the  treatment  is  satisfactory,  and 
that  there  is  no  necessity  to  increase  the  dose. 

MARRIAGE  AND  OFFSPRING 

Bayet  considers  that  as  regards  the  question  of 
marriage  and  offspring,  the  serum  diagnosis,  con- 
tagiousness, and  the  transmission  of  infection  to 
offspring  must  be  regarded  as  three  distinct  matters. 


120  SYPHILIS  AND  PARASYPHILIS 

He  thinks  that  clinical  experience  must  be  considered 
of  equal  value  with  the  Wassermann  reaction,  and 
the  question  of  date  of  infection,  length  and  nature  of 
treatment,  and  time  since  the  last  appearance  of  any 
symptoms,  must  be  thoroughly  gone  into  when  the 
practitioner  is  asked  his  advice  as  to  the  permissibility 
of  marriage.  He  does  not  consider  a  positive  Wasser- 
mann reaction  an  absolute  contra  indication  to  marriage, 
providing  that  all  other  considerations  are  satisfactory. 
If,  however,  marriage  of  a  man  giving  a  positive  re- 
action is  permitted  and  pregnancy  occurs,  he  advises 
that  the  mother  should  undergo  antisyphilitic  treat- 
ment even  if  she  presents  no  symptoms  and  gives 
a  negative  Wassermann  reaction. 

The  reaction  is  of  great  value  in  obstetric  practice 
as  a  means  of  diagnosing  latent  syphilis  in  the  mother, 
for  (if  positive)  then  energetic  antisyphilitic  treatment 
holds  out  great  hopes  of  the  birth  of  a  full-time  and 
healthy  child.  Bat  and  Daunay  consider  that  in  a 
pregnant  woman  one  solitary  negative  reaction  does 
not  authorize  the  conclusion  that  the  woman  is  free 
from  infection,  but  that  one  positive  reaction  is  diag- 
nostic of  certain  maternal  and  probable  fcetal  infection, 
and  indicates  active  treatment.  They  find,  when 
infection  has  occurred  some  time  after  conception, 
that  there  is  a  higher  percentage  of  positive  results 
with  the  mother  than  with  the  infant.  Treatment  of 
the  mother  during  pregnancy  produces  a  negative 
reaction  in  the  infant,  but  one  negative  reaction  does 
not  authorize  the  conclusion  that  the  infant  is  healthy 
and  can  be  suckled  by  a  healthy  wet-nurse.  CoUes's 
and  Prof  eta's  laws  have  been  proved  in  part  by  this 


CLINICAL   VALUE  OF  REACTION  121 

reaction.  The  immunity,  however,  of  the  mother  in 
Colles's  law  and  the  child  in  Profeta's  law  is  only- 
apparent  ;  they  cannot  contract  the  disease  because 
they  already  have  it  in  a  latent  form. 

Thomsen  and  Boas  examined  the  reaction  of  44 
newly  born  infants,  which  either  themselves  showed 
syphilitic  lesions  or  were  born  of  syphilitic  mothers, 
and  obtained  20  positive  and  24  negative  reactions. 
Sixteen  positive  cases  either  showed  clinical  evidence 
of  syphilis  within  three  months  or  died  in  the  interval, 
the  post-mortem  examination  showing  characteristic 
changes  in  the  organs.  In  the  remaining  4  positive 
cases  the  reaction  disappeared  completely,  and  did  not 
return  in  three  to  nine  months,  nor  did  these  cases 
develop  any  evidence  of  syphilitic  infection.  Of  the 
24  negative  cases,  17  remained  negative,  and  the 
infants,  during  a  period  of  observation  extending  over 
several  months,  showed  no  signs  of  disease.  Of  the 
mothers  of  these  17  infants,  10  gave  a  negative  reaction 
and  7  a  positive  reaction. 

Of  35  mothers  whose  children  showed  signs  of 
syphilis,  26  gave  a  positive  and  9  a  negative  re- 
action. 

Browning  and  Mackenzie  conclude  that  the  large 
majority  of  cases  with  a  positive  reaction  of  the  blood 
at  birth  subsequently  develop  symptoms  of  disease, 
and  that  the  large  majority  of  those  with  a  negative 
reaction  at  birth  remain  healthy.  They  also  consider 
that  the  examination  of  the  blood  from  the  mothers 
showed  that — 

I.  The  mother  may  be  positive  and  the  child 
negative. 


122  SYPHILIS  AND  PARASYPHILIS 

2.  The  mother  may  be  negative  and  the  child 
positive. 

3.  The  mother  and  child  may  both  be  positive. 

4.  The  mother  and  the  child  may  both  be  negative. 
As  regards  older  children,  Thomsen  and  Boas  found 

that  37  children  up  to  two  years  of  age  with  signs  of 
congenital  syphilis  all  gave  positive  reactions.  They 
further  found  that  of  27  older  children  and  adults  with 
manifestations  of  congenital  syphilis,  each  gave  a 
positive  reaction.  The  specific  affections  in  these 
latter  cases  included  interstitial  keratitis,  osteitis, 
choroiditis,  and  juvenile  general  paralysis. 

Accordingly,  a  negative  reaction  in  a  case  presenting 
active  lesions  is  strongly  against  the  latter  being  due 
to  congenital  syphilis. 

The  presence  of  the  positive  reaction  can  only  be 
held  to  denote  syphilis.  A  passive  absorption  of  the 
reaction  bodies  from  the  child  in  utero  is  excluded 
by  the  fact  that  the  reaction  is  not  transient,  but 
permanent. 

Probably  a  man  need  have  but  little  fear  for  the 
safety  of  his  children  so  long  as  his  wife  has  a  negative 
reaction. 


CHAPTER  XII 

SERUM  AND  CEREBRO-SPINAL  FLUID 
IN  NERVOUS  DISEASES 

GENERAL  PARALYSIS 

The  well-known  dogma,  '  General  paralysis  is  the 
product  of  syphilization  and  civilization,'  was  advanced 
by  Krafft-Ebing,  and  was  based  on  inoculation  ex- 
periments, in  which  he  found  that  general  paralytics 
invariably  gave  a  negative  result  when  inoculated 
with  syphilitic  virus. 

Many  authorities  consider  general  paralysis  and 
tabes  to  be  a  fourth  stage  in  syphilitic  infection,  but 
Mott  considers  that  there  is  a  primary  neuronic  decay 
which  cannot  be  accounted  for  solely  by  the  changes 
in  the  supporting,  enclosing,  and  nutrient  tissues. 
He  considers  that  the  pathology  of  parasyphilitic 
affections  is  that  in  certain  acquired  or  congenital 
syphilitic  individuals  the  durability  of  the  neurones 
is  greatly  curtailed,  so  that  they  decay  and  die  pre- 
maturely, thereby  giving  rise  to  a  series  of  symptoms 
which  may  be  associated  either  with  the  irritation  of 
definite  nerve  structures — e.g.,  lightning  pains,  visceral 
crises,  mania,  and  epileptiform  convulsions  ;  or  with 
neural  destructions — e.g.,   ataxy,    parassthesia,   anaes- 

123 


124  SYPHILIS  AND  PARASYPHILIS 

thesia,  paresis,  and  dementia.  The  irritative  phenomena 
may  be  the  sign  of  increased  neural  irritability  due  to 
degeneration  of  neurones  prior  to  their  death  and  loss 
of  function.  He  does  not,  however,  affirm  that  the 
lymphatic  and  vascular  changes  play  an  unimportant 
part  in  the  process  of  decay  and  death  of  the 
neurones. 

He  considers  that  if  the  Spivochceta  pallida  is  the 
cause  of  these  neuronic  degenerations  occurring  after 
a  lapse  of  an  average  of  ten  years,  this  is  only  to 
be  explained  by  the  existence  of  an  intracellular 
granular  resting  form  becoming  active  and  causing 
inflammatory  changes  in  the  membranes  and  vessels 
and  connective  tissues,  with  secondary  irritation  and 
destruction  of  the  neural  elements.  This  theory  he 
considers  purely  hypothetical,  and  one  that  cannot  be 
accepted  without  further  proof. 

He  points  out  that,  whereas  in  active  syphilis  giving 
a  positive  Wassermann  reaction  treatment  will  cause 
the  reaction  to  become  negative,  in  general  paralysis 
treatment  has  no  effect  on  the  Wassermann  reaction. 

Neisser  considers  that  the  late  manifestations  of 
syphilis  in  the  form  of  general  paralysis  or  tabes  may 
be  the  result  of  a  modification  of  the  action  of  the 
specific  organism  by  the  widespread  use  of  mercury, 
and  others  have  put  forward  the  suggestion  that  there 
may  be  a  specific  spirochsete  for  these  diseases. 

Whereas  some  strains  of  spirochaetes  seem  to  affect 
bone  and  viscera,  others  appear  to  chiefly  attack  the 
central  nervous  system.  Both  Brosius  and  Erb  quote 
cases  in  which  several  individuals  were  infected  from 
one  source,  and  in  which  the  majority  of  those  infected 


NERVOUS  DISEASES  125 

developed  later  either  general  paralysis  or  tabes ;  and 
cases  of  general  paralysis  or  tabes  occurring  in  both 
husband  and  wife  appear  to  be  more  common  than 
can  be  accounted  for  by  coincidence. 

Browning  and  Mackenzie,  in  reviewing  the  work 
of  Mott  and  Spielmeyer,  emphasize  the  resemblance 
between  lesions  of  the  central  nervous  system  pro- 
duced by  dourine,  by  experimental  trypanosome 
infection  in  dogs,  and  by  sleeping-sickness,  and  the 
lesions  produced  in  parasyphilitic  conditions.  The 
lesions  of  the  central  nervous  system  in  dourine,  in 
the  dogs  experimented  on,  and  in  sleeping-sickness, 
were  all  produced  by  a  trypanosome,  and  these  lesions 
were  very  like  those  found  in  parasyphilis.  They 
therefore  conclude  that  it  seems  highly  probable  not 
only  that  parasyphilis  is  caused  by  the  Spirochceta 
pallida,  but  also  that  the  Spivochcdta  pallida  is  a 
protozoon. 

In  countries  where  syphilis  has  recently  been  intro- 
duced, and  the  disease  often  takes  a  malignant  form, 
general  paralysis  is  almost  unknown  ;  and  it  has 
been  suggested  that  general  paralysis  and  tabes  may 
be  the  result  of  a  partial  immunity  arising  in 
populations  which  for  several  generations  have  been 
infected. 

Blood  in  General  Paralysis.  —  Plant,  Mott, 
Chandler,  and  many  other  workers  agree  that  a  positive 
Wassermann  reaction  is  given  by  the  blood  of  prac- 
tically all  general  paralytics. 

Of  156  cases  examined  by  Plant,  all  were  positive; 
and  of  64  cases  examined  by  Mott,  Chandler,  and 
Henderson-Smith,  92  per  cent,  were  positive.     Boas 


126  SYPHILIS  AND  PARASYPHILIS 

obtained  positive  results  in  every  case  in  139  cases 
examined. 

Plaut  points  out  that  other  syphilitic  affections, 
even  in  the  florid  stage,  exhibit  no  such  complete 
regularity  in  reaction,  and  he  considers  that  general 
paralysis  occupies  in  respect  to  the  Wassermann 
reaction  a  unique  position  among  all  the  varied 
clinical  forms  of  syphilis.  He  considers  that  we  may 
have  to  count  on  the  possibility  that  perhaps  the 
syphilitics  who  lack  the  reaction  in  the  florid  stage 
have  no  tendency  to  develop  paresis  later,  and  that 
therefore  the  production  of  the  reacting  substance 
represents  a  primary  condition  in  the  development 
of  a  metasyphilitic  disease.  He  considers  that  the 
existence  of  general  paralysis  can  practically  be 
excluded  if  the  serum  of  the  patient  gives  a  negative 
Wassermann,  and  that  general  paralysis  is  the  only 
one  of  all  the  syphilitic  afliections  in  which  a  negative 
result  is  of  definite  clinical  value.  He  points  out  that 
for  differential  diagnosis  the  negative  result  is  of  more 
importance  than  the  positive ;  for,  while  a  negative 
finding  excludes  the  diagnosis  of  general  paralysis,  a 
positive  reaction  proves  absolutely  nothing  concerning 
general  paralysis,  but  simply  shows  that  the  patient 
has  had  syphilis.  He  therefore  advises  in  every  case 
in  which  general  paralysis  is  suspected  that  the  blood 
should  be  first  examined,  and,  if  the  result  is  negative, 
that  lumbar  puncture  should  not  be  proceeded  with. 
If,  however,  a  positive  result  is  obtained  in  the  blood, 
lumbar  puncture  should  then  be  performed  for  the 
purpose  of  biological  and  cytological  examination  of 
the  cerebro-spinal  fluid. 


NERVOUS  DISEASES 


127 


Cerebro-Spinal  Fluid  in  General  Paralysis.— 

Plaut  considers  that,  with  few  exceptions,  there  is 
a  positive  Wassermann  reaction  and  an  increase  in 
the  lymphocyte  count. 

Of  154  cases  examined,  all  of  which  gave  a  positive 
Wassermann  with  the  blood,  146  cases  gave  a  posi- 
tive reaction  of  the  cerebro-spinal  fluid,  2  a  doubtful 
reaction,  and  6  a  negative  reaction  ;  146  gave  a 
lymphocytosis,  and  8  showed  no  cell  increase. 

General  Paralylis,   154  Cases  (Plaut). 


Number  of 
Cases. 

Blood  (Wasser- 
mann Reaction). 

Cerebro-Spinal 
Fluid  (Wasser- 
mann Reaction). 

Cytology. 

138 

6 
2 

8 

+ 

+ 
+ 

+ 

+ 

+ 

+ 
+ 
+ 

100  per  cent. 

95  per  cent. 

95  per  cent. 

The  lymphocytosis  in  general  paralysis,  according 
to  most  observers,  is  not  influenced  by  antisyphilitic 
treatment. 

Chandler  reports  that  in  80  cases  diagnosed  as 
general  paralysis,  in  which  the  cerebro-spinal  fluid 
was  withdrawn  during  life  by  lumbar  puncture  and 
examined  by  the  Wassermann  test,  the  clinical 
diagnosis  has  been  controlled  by  post-mortem  ex- 
amination ;  67  cases  gave  a  positive  reaction,  and 
the  post-mortem  examination  showed  the  character- 
istic changes  of  general  paralysis.     Of  the  13  cases 


128  SYPHILIS  AND  PARASYPHILIS 

that  failed  to  give  a  positive  Wassermann,  2  were 
found  at  the  post-mortem  examination  to  be  cases  of 
general  paralysis :  the  remaining  1 1  were  shown  by 
the  post-mortem  examination  not  to  be  cases  of 
general  paralysis,  although  in  six  of  them  this  con- 
dition was  diagnosed  by  the  clinical  symptoms. 

In  another  series  of  six  cases  which  gave  a  negative 
reaction  with  the  cerebro-spinal  fluid,  although  general 
paralysis  had  been  diagnosed,  in  every  case  the  sub- 
sequent progress  of  the  cases  showed  that  the  diagnosis 
had  been  erroneous.  Five  of  these  were  discharged 
cured,  the  remaining  case  being  finally  diagnosed  as 
dementia  prsecox. 

Chandler  concludes  that  a  positive  reaction  cannot 
be  obtained  in  the  cerebro-spinal  fluid  except  in 
general  paralysis  and  tabes  and  in  a  few  rare  cases 
of  syphilis  of  the  central  nervous  system.  He  con- 
siders that  in  all  cases  an  excess  of  lymphocytes 
indicates  an  organic  disease,  but  not  necessarily  either 
syphilis  or  parasyphilis.  He  thinks  that  a  positive 
reaction  of  the  cerebro-spinal  fluid  in  conjunction 
with  a  lymphocytosis  points  much  more  strongly 
to  parasyphilis,  especially  general  paralysis,  than  to 
cerebral  syphilis  or  spinal  syphilis. 

He  considers  that  if  there  is  a  positive  reaction  with 
the  serum  associated  with  nervous  or  mental  pheno- 
mena, lumbar  puncture  should  be  performed;  and  if 
the  cerebro-spinal  fluid  gives  a  positive  reaction,  the 
indication  is  strongly  in  favour  of  general  paralysis. 


NERVOUS  DISEASES  129 

TABES  DORSALIS 

The  Wassermann  reaction  is  not  nearly  of  as  much 
value  in  the  diagnosis  of  tabes  as  in  general  paralysis, 
since  a  positive  reaction  is  only  obtained  in  the  blood 
in  about  60  per  cent,  of  cases,  and  in  the  cerebro- 
spinal fluid  in  only  about  50  per  cent.  Cases  some- 
times occur  in  which  a  positive  reaction  is  present  in 
the  cerebro-spinal  fluid  and  not  in  the  blood. 

A  pathological  increase  in  the  lymphocytes  is  also 
found  in  only  about  60  per  cent,  of  cases. 

It  therefore  follows  that,  though  a  positive  Wasser- 
mann reaction  in  the  blood  and  cerebro-spinal  fluid 
accompanied  by  a  cellular  increase  may  be  of  con- 
siderable diagnostic  value,  yet  a  negative  reaction 
cannot  put  tabes  out  of  court. 

Of  43  cases  examined  by  Boas,  28  were  positive 
and  15  negative.  If  these  cases  v;ere  given  under  the 
headings  of  '  treated  '  and  '  untreated '  cases,  it  would 
be  found  that  of  the  17  cases  that  did  not  receive 
treatment  all  were  positive,  whereas  of  the  26  cases 
which  had  received  treatment  11  were  positive  and 
15  negative. 

Of  36  cases  examined  by  Browning  and  Mackenzie, 
72  per  cent,  gave  a  positive  reaction  with  the  serum. 

Of  50  cases  examined  by  the  author,  30  (60  per 
cent.)  were  positive. 

CEREBRAL  SYPHILIS 

In  this  condition  a  positive  reaction  is  usually  given 
with  the  serum,  but  not  with  the  cerebro-spinal  fluid. 
Of  18  cases  examined  by  Plant,  14  were  positive 

9 


130  SYPHILIS  AND  PARASYPHILIS 

with  the  serum  and  negative  with  the  cerebro-spinal 
fluid,  3  were  positive  with  both  serum  and  cerebro- 
s^pinal  fluid,  and  i  was  negative  with  both. 

Nonne,  however,  obtained  a  positive  reaction  in  the 
cerebro-spinal  fluid  in  4  out  of  16  cases  examined. 

Mott  considers  that  25  per  cent,  give  a  positive 
reaction  with  the  cerebro-spinal  fluid,  and  that  most 
of  the  cases  show  a  well-marked  lymphocytosis. 

MENTAL  DEFICIENCY 

Still  found  six  idiots  amongst  142  consecutive  cases 
of  congenital  syphilis  (4-2  per  cent.).  He  considers 
that  the  proportion  of  cases  of  idiocy  due  to  syphilis 
would  be  considerably  higher  if  mental  degeneration, 
as  an  acquired  condition  beginning  after  some  years 
of  apparently  normal  mental  power,  were  included. 

Tredgold  found  definite  clinical  evidence  of  syphilis 
in  2 "5  per  cent,  of  cases  out  of  150  inmates  of  idiot 
asylums.  Doubtless  the  Wassermann  reaction  would 
have  greatly  raised  the  percentage  of  cases  demon- 
strable as  syphilitic  in  this  series. 

Of  36  cases  examined  by  Plant,  23  gave  a  positive 
Wassermann  ;  in  only  10  cases  was  the  cerebro-spinal 
fluid  examined,  and  these  included  4  cases  of  general 
paralysis,  which  were  all  positive,  and  2  cases  of 
acute  cerebral  syphilis,  which  were  both  positive ; 
2  cases  of  secondary  syphilis,  and  2  cases  of  meningo- 
coccus meningitis  with  manifest  hereditary  syphilis, 
were  both  negative. 

In  a  very  interesting  series  of  330  cases  of  congenital 
mental  deficiency  examined  by  Dean,  55  gave  a  posi- 


NERVOUS  DISEASES  131 

tive  Wassermann  reaction — namely,  15-5  per  cent. 
Among  the  55  positive  cases  there  were  13  which 
showed  other  evidence  of  syphilitic  infection. 


DIFFERENTIAL   DIAGNOSIS 

Individuals  who  have  contracted  syphilis  occasion- 
ally develop  hysteria,  hypochondriasis,  or  syphilo- 
phobia,  and  in  such  cases,  as  Mott  points  out,  a 
negative  Wassermann  reaction  may  be  able  to  allay 
their  ungrounded  fears  and  their  desire  for  salvarsan 
treatment. 

Neurotics  suffering  with  arterio-sclerosis  may  become 
melancholic  and  irritable,  and  develop  symptoms  sug- 
gesting general  paralysis.  Examination  of  the  cerebro- 
spinal fluid  will  at  once  settle  the  diagnosis. 

Mott  considers  that  parasyphilitic  affections  may  be 
definitely  differentiated  from  neurasthenic  conditions 
by  an  examination  of  the  cerebro-spinal  fluid,  and  that 
a  lymphocytosis  points  definitely  to  a  chronic  inflam- 
matory condition  of  the  central  nervous  system,  of 
which,  however,  syphilis  may  not  be  the  only  cause. 

Chronic  alcoholism  and  syphihs  are  so  often  associ- 
ated that  cases  frequently  occur  in  which  there  is 
considerable  difficulty  of  diagnosis  from  general 
paralysis.  A  negative  Wassermann  in  these  cases 
will  exclude  general  paralysis  ;  but  if  the  reaction  is 
positive,  and  the  symptoms  suggest  the  possibility  of 
general  paralysis  or  syphilitic  disease  of  the  central 
nervous  system,  recourse  should  be  had  to  lumbar 
puncture. 

One  must  not  lose  sight  of  the  diagnostic  value  of 


132  SYPHILIS  AND  PARASYPHILIS 

the  influence  of  treatment  on  lymphocytosis  of  the 
cerebro-spinal  fluid.  It  is  difficult  to  diagnose  between 
syphilitic  cerebro-spinal  meningitis,  tabes,  and  general 
paralysis.  In  all  three  conditions  there  may  be  a  high 
lymphocytosis,  and  a  positive  Wassermann  may  be 
present,  though  rarely  in  the  syphilitic  cerebro-spinal 
meningitis,  as  well  as  in  parasyphilitic  conditions.  If, 
however,  after  a  short  course  of  mercurial  inunctions 
or  intramuscular  injections,  a  rapid  fall  in  the  number 
of  leucocytes  in  the  cerebro-spinal  fluid  is  recorded, 
parasyphilis  can  be  excluded. 

In  toxic  peripheral  neuritis  with  ataxia  the  symptoms 
may  be  confused  with  those  of  tabes.  Examination  of 
the  cerebro-spinal  fluid,  however,  will  settle  the  diag- 
nosis. The  reaction  will  be  negative,  and  there  will 
be  no  lymphocytosis. 

Mott  is  of  the  opinion  that  a  person  suffering  with 
an  affection  of  the  nervous  system,  whose  blood  gives 
a  positive  serum  reaction,  is  much  more  likely  to  be 
suffering  from  a  syphilitic  affection  than  one  who  has 
had  syphilis^  but  whose  blood  does  not  yield  the 
reaction.  An  examination  of  the  cerebro-spinal  fluid 
in  such  a  case  will  afford  most  valuable  evidence,  and 
he  considers  that  srich  evidence  is  of  vital  importance. 

In  the  case  of  acute  syphilitic  disease,  antisyphilitic 
treatment  will  cause  a  disappearance  of  the  Wasser- 
mann reaction  and  of  the  lymphocytosis  in  the  cerebro- 
spinal fluid.  There  will  be  either  cure  or  improvement 
in  the  symptoms. 

In  the  case  of  general  paralysis  or  tabes,  especially 
general  paralysis,  however,  both  the  serum  and 
cerebro-spinal  fluid  will  give  a  positive  Wassermann, 


NERVOUS  DISEASES 


133 


which  will  be  uninfluenced  by  treatment,  and  in  the 
majority  of  cases  the  lymphocytosis  of  the  cerebro- 
spinal fluid  will  not  be  improved  by  the  treatment. 

Hysteria,  hystero-epilepsy,  neurasthenia,  chronic 
alcoholism,  dementia  praecox,  disseminated  sclerosis, 
tubercular  meningitis,  and  cerebral  abscess,  will  all 
give  negative  Wassermann  reactions  of  the  blood 
except  in  those  cases  in  which  a  syphilitic  affection 
may  be  coincident,  but  none  will  give  a  positive 
Wassermann  of  the  cerebro-spinal  fluid. 

Paraplegia,  hemiplegia,  cerebral  tumour,  meningitis, 
or  idiocy,  may  be  syphilitic  in  origin.  An  examina- 
tion of  the  blood  and  cerebro-spinal  fluid  will  be 
of  great  importance  for  arriving  at  appropriate  treat- 
ment. 

The  following  tables  give  the  relation  between 
the  diagnosis  of  tabes  and  general  paralysis  and  the 
Wassermann  reaction  of  the  blood  and  cerebro-spinal 
fluid  as  recorded  by  various  observers  : 


Table  III. 


Diagnosed  as  Tabes. 

Diagnosed  as  General 
Paralysis. 

Serum. 

Cerebro- 
spinal Fluid. 

Serum. 

Cerebro- 
spinal Fluid. 

v.z, 

u.t: 

,Q  in 
a  « 

|u 

U.t! 

■     t" 

it  « 

io 
12; '0 

a,  Oh 

1=1    «S 

^'0 

O.ti 

Noguchi 

Marie  and  Levaditi 
Wassermann 
Mott,  Chandler,  and 
Henderson-Smith 

Bayly 

Plaut 

205 
50 

60 
60 

II 
9 

20 

54 
66 

53 
45 

61 

20 

150 

65 

85 
100 

60 

35 

64 

8 

150 

73 
94 

92 
87 
96 

134 


SYPHILIS  AND  PARASYPHILIS 
Table  IV. 


The  Wassermann  Reaction  of  the  Blood  in 
Nervous  Diseases  other  than  General 
Paralysis  and  Tabes  (Author's  Series). 


Diagnosis. 

Number  of 
Cases. 

Per  Cent. 
Positive. 

Cerebral  tumour 

31 

24 

Paraplegia 
Hemiplegia' 
Pachymeningitis 
Disseminated  sclerosis 

25 
16 
16 
13 

24 
25 
25 
15 

Epilepsy   . . 
Optic  atrophy 
Mental  Deficiency 

10 
4 
4 

0 

75 
50 

CHAPTER     XIII 

TREATMENT 

SALVARSAN 

DioxY-DiAMiDO-ARSENo-BENZoL  ("  6o6  "),  discovered  by 
Ehrlich  and  Hata  in  1909,  not  by  chance,  but  as  the 
direct  outcome  of  long  and  patient  research,  is  now 
universally  recognized  as  one  of  the  most  potent  anti- 
syphilitic  remedies.  Like  all  new  remedies,  it  has  its 
strong  advocates  and  equally  strong  detractors.  It 
has  now  passed  through  the  fire  of  most  searching 
criticism,  and  has  emerged  from  the  experimental  stage 
to  permanently  take  its  place  amongst  the  most 
valuable  antisyphilitic  remedies.  Its  remarkable 
efficacy  in  clearing  up  syphilitic  manifestations  has 
been  established,  and,  though  at  present  it  is  impossible 
to  state  that  any  given  number  of  injections  with 
salvarsan  will  definitely  cure  every  case  of  syphilis, 
still  we  know  that  in  the  vast  majority  of  cases  it  has 
great  therapeutic  value.  It  would  be  as  foolish  to  say 
that  salvarsan  is  useless  because  it  does  not  perman- 
ently cure  with  two  or  three  injections  as  to  say  that 
mercury  is  useless  because  two  years  of  pill  treatment, 
or  two  courses  of  inunctions  or  intramuscular  injections, 
do  not  produce  permanent  cure  in  the  majority  of  cases. 

135 


136  SYPHILIS  AND  PARASYPHILIS 

In  every  case  of  microbic  invasion  we  have  to  con- 
sider a  variety  of  factors — variations  in  strain  of  the 
invading  organism,  the  soil,  and  the  reaction  of  the 
individual  to  the  infection.  Syphilis  is  no  exception  to 
this  general  rule,  and  it  is  not  to  be  wondered  at  that 
no  two  cases  behave  in  a  precisely  similar  manner 
either  towards  the  infecting  agent  or  towards  the 
remedy  prescribed  to  combat  it.  In  no  given  case  can 
the  progress  of  the  syphilitic  infection  be  foreseen,  and 
no  one  who  undertakes  the  treatment  of  a  primary 
lesion  can  predict  the  course  that  will  be  taken  by  the 
disease. 

Method  of  Administration. 

Apparatus. — The  apparatus  used  by  the  author 
consists  of  a  container  surrounded  by  a  hot-water 
jacket ;  a  rubber  tube  about  4  feet  long,  which  connects 
the  container  and  the  needle-holder ;  and  a  stout  needle 
I J  inches  long  and  of  the  calibre  of  a  fine  exploring 
needle.  About  3  inches  from  the  needle-holder  a  piece 
of  glass  tubing  is  let  in  to  act  as  a  window.  The  con- 
tainer, tube,  and  needle-holder  are  connected  up  and 
sterilized  before  use.  The  rate  of  flow  is  regulated  by 
altering  the  height  of  the  container,  and  a  clip  is 
applied  to  the  rubber  tube  about  a  foot  from  the  needle- 
holder  (Fig.  21). 

Technique. — The  patient  should  be  in  bed,  with 
the  arm  selected  for  the  infusion  supported  on  a  pillow. 
Having  sterilized  in  the  autoclave  a  glass  measure 
graduated  to  300  c.c.  and  also  a  glass  stirring  rod, 
100  c.c.  of  sterilized  normal  saline  is  poured  into 
the  measure.     The  end  of  the  phial  containing  the 


Fig,  21. 

Apparatus  for  Intravenous  Injection  of  Salvarsan 
(Author's  Pattern). 


138  SYPHILIS  AND  PARASYPHILIS 

salvarsan  is  now  broken  off,  and  the  contents  are 
slowly  shaken  into  the  saline,  which  is  briskly  stirred. 
A  clear  yellow  acid  solution  results.  Sterilized  normal 
sodium  hydrate  solution  is  now  added  slowly  drop  by 
drop,  till  the  yellow  precipitate  which  is  first  produced 
is  just  redissolved.  More  normal  saline  solution  is 
now  added  to  bring  the  volume  up  to  300  c.c.  All  the 
solutions  employed  should  be  at  a  temperature  of 
110°  F.  The  water-jacket  surrounding  the  irrigator  is 
also  filled  with  water  at  a  temperature  of  1 10°  F.  The 
irrigator  is  now  filled  with  warm  saline  solution,  which 
is  run  through  till  all  air-bubbles  have  been  got  rid  of. 
The  clip  is  now  applied  and  the  needle-holder  put  into 
the  sterilized  tumbler  containing  some  warm  sterile 
saline  solution.  The  skin  over  the  most  prominent 
vein  at  the  bend  of  the  elbow  is  sterilized  by  dabbing 
it  with  a  saturated  solution  of  iodine  in  chloroform  and 
a  bandage  applied  firmly  round  the  upper  arm  in  order 
to  distend  the  vein.  If  the  veins  are  small  the  arm 
must  be  soaked  in  hot  water  for  a  few  moments,  and 
the  patient  told  to  clasp  and  unclasp  his  hand.  The 
needle,  having  been  boiled,  is  now  adjusted  to  the 
holder  and  a  little  saline  solution  run  through.  The 
irrigator  is  now  lowered  and  the  needle  plunged  into 
the  vein  and  the  clip  removed.  If  the  needle  is  in  the 
vein  the  blood  will  run  into  the  tube  and  be  seen  at  the 
*  window.'  The  bandage  is  now  removed  and  the 
irrigator  raised,  and  about  50  c.c.  of  the  saline  allowed 
to  run  in.  If  no  local  swelling  is  produced,  the  required 
quantity  of  the  solution  of  salvarsan  can  now  be  poured 
in.  If,  however,  any  local  swelling  is  produced  by  the 
saline,  the  needle  must  be  removed  and  the  procedure 


TREATMENT  139 

recommenced  in  another  vein.  The  solution  should 
only  be  allowed  to  run  in  slowly  so  as  to  be  well  diluted 
by  the  blood-stream,  and  it  should  take  about  ten 
minutes  to  run  in  all  the  solution.  o'6  gramme  of 
salvarsan  having  been  diluted  up  to  300  c.c,  50  c.c.  of 
the  diluted  fluid  contains  o'l  gramme  of  salvarsan. 
0'6  gramme  is  the  author's  usual  dose  for  a  healthy 
male  adult  and  o'5  gramme  for  a  woman.  About 
100  c.c.  of  normal  saline  solution  should  be  poured  into 
the  irrigator  when  the  salvarsan  solution  has  almost 
run  out,  so  that  the  needle  may  be  washed  free  of 
salvarsan  before  being  withdrawn  ;  otherwise  some 
salvarsan  may  escape  along  the  needle  track  and  pro- 
duce some  local  inflammation  and  possibly  phlebitis 
and  thrombosis. 

Preparation  of  the  Patient.— The  preparation  of 
the  patient  is  of  great  importance,  as,  if  the  infusion  is 
given  with  a  full  stomach  and  high  blood-pressure,  an 
alarming  condition  of  feeble  rapid  pulse  and  collapse 
may  supervene,  which,  however,  usually  passes  off 
when  vomiting  occurs.  Rigors  are  not  uncommon  in 
florid  syphilis,  and  may  occur  from  one  to  three  hours 
after  the  infusion.  The  patient  sometimes  complains 
of  throbbing  in  the  head  and  a  metallic  taste  in  the 
mouth  and  a  sense  of  fulness  in  the  throat.  The 
author  prepares  the  patient  by  giving  a  pill  the  night 
before  and  a  brisk  saline  purge  on  the  morning  of  the 
infusion.  Only  a  light  breakfast  is  allowed,  with  but 
little  fluid  and  no  food  or  drink  for  four  hours  before  the 
infusion.  Since  the  author  has  adopted  these  precau- 
tions he  has  recorded  no  alarming  symptoms. 


I40  SYPHILIS  AND  PARASYPHILIS 

Dosage. 

The  question  of  dosage  and  mode  of  administration 
appear  to  be  of  vital  importance,  and  the  experiments 
of  Hata  carried  out  upon  animals  lend  great  support 
to  this  view.  In  mice  inoculated  with  organisms  of 
relapsing  fever,  a  single  injection  of  g^y  gramme 
(per  20  grammes  of  weight)  of  salvarsan  gave  100  per 
cent,  of  cures,  while  the  administration  of  half  this 
dose  was  followed  by  82  per  cent,  of  failures. 
Similarly,  suggestive  results  were  obtained  in  '  syphil- 
ized '  rabbits  with  scrotal  chancres,  0-0075  P^^  kilo- 
weight  effecting  complete  cure,  while  0*004  gramme 
proved  ineffective. 

The  usual  dose  for  adults  given  by  the  intravenous 
route  is  0*5  gramme  for  a  woman,  and  0*6  gramme  for 
a  man. 

In  the  absence  of  temperature  and  nephritis,  the 
author  repeats  the  dose  after  forty-eight  hours. 

Therapeutic  Results. 

I.  Primary  Syphilis.— In  the  majority  of  primary 
cases  the  effect  of  salvarsan,  whether  administered  by 
the  intramuscular  or  the  intravenous  route,  is  prompt, 
and  some  degree  of  softening  of  the  hard  chancre  is 
frequently  observed  within  twenty-four  hours.  Accord- 
ing to  Wechselmann,  eroded  chancres  become  clean 
after  from  twelve  to  twenty-four  hours,  and,  further, 
the  Spivochceta  pallida  is  no  longer  found  in  scrapings 
taken  after  one  or  two  days.  The  rapidity  with  which 
absorption  takes  place  depends  upon  several  factors  — 


TREATMENT  141 

the  degree  of  induration  present,  the  actual  size  of  the 
lesion,  and  the  dose  of  the  drug  exhibited. 

Gibbard,  Harrison,  and  Cane,  in  order  to  compare 
the  effect  of  salvarsan  with  that  of  mercury  in  prevent- 
ing the  onset  of  secondary  symptoms  when  treatment 
was  commenced  in  the  primary  stage,  treated  38  cases 
of  primary  sore  with  salvarsan,  and  another  series  of  a 
similar  38  cases  with  mercurial  injections.  In  all 
cases  the  Spivochceta  pallida  had  been  demonstrated. 
All  the  cases  were  under  observation  for  at  least  four 
months.  Of  the  38  salvarsan-treated  cases,  only  2 
(5*2  per  cent.)  developed  secondary  symptoms,  while 
of  the  38  mercury-treated  cases,  36  (94 "8  per  cent.) 
developed  secondary  symptoms. 

These  extremely  valuable  parallel  investigations  in 
strictly  comparable  cases  emphasize  clearly  and 
beyond  all  doubt  the  very  great  importance  of  the 
early  administration  of  salvarsan. 

2.  Secondary  Syphilis. — As  regards  the  effect  of 
salvarsan  on  the  manifestations  of  secondary  syphilis, 
it  is  almost  impossible  to  write  a  critical  report,  as  the 
innumerable  contributors  to  the  literature  are  almost 
unanimously  in  favour  of  the  drug.  Ernest  Lane  and 
C.  F.  Marshall  of  this  country,  working  independently, 
and  Engmann,  Mark,  and  Marchildon,  working 
together,  consider  that  equally  good  effects  can  be 
obtained  with  mercurial  treatment.  These  observers, 
however,  had,  when  they  first  advanced  these  opinions, 
personal  experience  of  only  quite  a  small  number  of 
salvarsan-treated  cases,  and  probably  with  efficient 
doses  given  by  the  intravenous  route  their  future 
reports   will   not   be   so    pessimistic.     Ernest    Lane, 


142  SYPHILIS  AND  PARASYPHILIS 

indeed,  has  already  modified  the  opinions  he  first 
expressed,  which  were  that  intolerance  to  mercury 
would  be  the  only  justification  for  looking  elsewhere 
for  a  remedy. 

As  is  to  be  expected,  secondary  manifestations  differ 
very  considerably  in  their  reaction  to  salvarsan,  and 
sclerosed  lesions  take  much  longer  to  resolve  than  soft 
conditions,  such  as  mucous  plaques,  condylomata,  and 
superficial  ulceration  of  the  mucous  membrane,  which 
usually  disappears  in  twenty-four  to  forty-eight  hours, 
Wechselmann  stating  in  respect  to  mucous  plaques 
of  the  mouth,  '  even  if  the  patient  smokes  con- 
tinuously.' 

The  pains  arising  from  secondary  syphilitic  infection 
of  periosteum  or  joints  are  frequently  relieved  in  an 
extraordinarily  short  time,  and,  indeed,  pain  of  any 
kind  arising  during  the  course  of  syphilis,  either  early 
or  late,  is  usually  most  favourably  influenced  by 
salvarsan. 

It  is  particularly  in  malignant  syphilis,  reacting  little 
or  not  at  all  to  mercurial  treatment,  that  the  value  of 
salvarsan  is  most  strikingly  seen.  Numerous  cases  are 
recorded  of  patients  apparently  doomed  to  death,  owing 
to  the  entire  failure  of  mercury  to  check  the  morbid 
processes,  who  have  been  saved  by  the  administration 
of  salvarsan. 

Gibbard  and  Harrison  found  that  of  thirty-two  cases 
which  were  either  uninfluenced  by  or  intolerant  to 
mercury,  all  but  one  were  to  all  appearance  com- 
pletely cured  by  salvarsan.  Intolerance  to  mercury 
on  the  part  of  the  patient  and  immunity  to  mercury 
on  the  part  of  the  spirochaete  being  rare,  the  cases 


TREATMENT  143 

recorded  by  these  officers,  which  were  collected  from 
all  the  military  stations  of  Great  Britain  and  Ireland, 
are  of  extreme  interest  and  value. 

3.  Tertiary  Syphilis. — In  no  stage  of  syphilis  is 
improvement  by  salvarsan  more  marked  than  in  the 
tertiary,  and  there  can  be  few  clinicians  with  any  con- 
siderable experience  of  Ehrlich's  specific  who  have  not 
met  cases  of  severe  and  intractable  ulcerations,  or  bone 
lesions,  in  which  the  new  treatment  acted  '  like  a 
charm.'  Within  a  few  hours  the  symptoms  begin  to 
subside,  and  within  one  to  three  weeks  not  only  have 
the  lesions  healed,  but  the  patient's  general  condition 
has  also  remarkably  improved.  Cases  of  chronic 
superficial  glossitis  have  been  most  successfully  treated 
by  salvarsan. 

The  author's  own  experience  but  confirms  the 
results  reported  by  previous  contributors  to  the 
literature,  and  only  adds  to  the  indisputable  evidence 
as  to  the  value  of  salvarsan  in  removing  the  symptoms 
of  tertiary  syphilis. 

4.  Congenital  Syphilis. — The  opinion  as  to  the 
value  of  the  drug  in  interstitial  keratitis  is  still  divided, 
and  it  is  only  to  be  expected  that  the  least  effect  would 
be  produced  in  non-vascular  tissue,  such  as  the  cornea. 
Infants  under  six  months  should  not,  by  preference, 
be  treated  directly,  on  account  of  the  enormous  number 
of  spirochaetes  present  and  the  large  quantity  of  endo- 
toxin set  free  by  an  efficient  dose  of  salvarsan,  but 
indirectly  through  the  milk  of  the  mother  who  has 
been  treated.  If  the  mother  cannot  feed  her  baby,  so 
that  treatment  via  the  milk  is  impossible,  intramuscular 
injection  of  not  more  than  0-02  gramme  may  be  given 


144  SYPHILIS  AND  PARASYPHILIS 

to  newly  born  infants  in  urgent  cases,  or  if  the  child  is 
several  months  old,  McDonagh  does  not  think  0*004 
to  0-005  gramme  per  pound  weight  of  child  to  be  too 
large  a  dose. 

Pregnant  women,  if  healthy,  may  with  safety  be 
treated,  and  Wechselmann  has  reported  a  case  injected 
five  weeks  before  delivery,  in  which  an  apparently 
healthy  baby  with  a  negative  Wassermann  reaction 
was  born. 

5.  Parasyphilis. — (i)  Tabes. — The  evidence  that 
has  accumulated  as  to  the  value  of  salvarsan  in  early 
cases  of  tabes  is  considerable.  Not  every  case,  how- 
ever, benefits  from  the  treatment,  and,  indeed, 
occasionally  an  exacerbation  of  symptoms  has  been 
noticed.  The  rule,  however,  seems  to  be  that  there  is 
diminution  in  the  pain,  ataxia,  and  frequency  of  crises 
with  improvement  in  general  health,  and  of  the 
bladder  and  rectal  symptoms. 

Wechselmann  and  McDonagh  have  each  reported  a 
case  in  which  return  of  sexual  power  has  followed 
treatment,  and  have  noticed  in  a  few  cases  a  return 
of  mobility  in  rigid  pupils  and  of  the  patella  reflex. 
Wechselmann  writes  :  *  In  view  of  extensive  subjective 
improvements  I  no  longer  hesitate  to  administer 
injections,  even  in  cases  where  the  Wassermann 
reaction  is  negative.  Undoubtedly  an  important 
part  in  this  happy  result  should  be  attributed  to  the 
stimulating  and  tonic  effect  of  the  remedy.  We  cannot 
for  some  years  conclude  that  the  remedy  permanently 
stops  the  progress  of  the  disease.' 

Out  of  a  large  number  of  cases  treated  by  James 
Collier,  he  has  recorded  no  permanent  ill-effect  referable 


TREATMENT  145 

to  the  medication,  and  no  aggravation  of  the  tabetic 
symptoms  after  injection.  In  the  majority  of  cases 
marked  improvement  in  general  health,  nutrition, 
colour,  and  feeling  of  well-being  occurred  within  a 
couple  of  weeks  of  the  injection. 

The  ataxy  improved  conspicuously  in  several  cases, 
and  occasionally  sphincter  trouble  seemed  benefited ; 
on  the  other  hand,  he  did  not  see  any  of  the  character- 
istic physical  signs  of  the  disease  disappear  entirely. 
In  those  cases  where  pains  were  present  and  trouble- 
some, very  striking  relief  followed  the  salvarsan 
injection.  Four  patients,  who  suffered  from  severe 
gastric  crises,  improved  remarkably. 

The  results  obtained  suggest  that  salvarsan  may  be 
of  considerable  value  in  the  treatment  of  tabes,  especi- 
ally in  early  cases  occurring  soon  after  infection. 

Marcus  concludes  that  'we  are  certain  now  that 
salvarsan  is  very  useful  in  syphilitic  nervous  diseases, 
and  that  it  acts  more  rapidly  and  is  more  convenient 
than  mercury  or  potassium  iodide.'  He  thinks  it 
justifiable  to  give  salvarsan  even  in  advanced  cases  of 
tabes,  as  it  may  ameliorate  the  pains  and  lengthen 
life,  although  there  may  be  no  hope  of  cure. 

(2)  General  Paralysis.  —  A  few  cases  of  apparent 
recovery  following  injection  with  salvarsan  have  been 
reported.  Treupel  has  frequently  noticed  a  transient 
improvement.  Most  writers,  however,  report  complete 
absence  of  improvement,  and  the  cases  that  are  bene- 
fited must  be  few.  Still,  in  the  light  of  occasional 
successes,  early  cases  should  be  given  the  chance  of 
cure  or  improvement,  even  if  this  be  an  extremely 
small  one. 

10 


146  SYPHILIS  AND  PARASYPHILIS 

Dangers. 

Toxicity. — Professor  Ehrlich,  after  investigating 
reports  of  10,000  cases,  stated  that  only  a  single  fatal 
case  had  been  recorded  in  which  the  patient's  life  had 
not  been  directly  in  danger  from  the  disease  itself. 
In  this  connection  it  is  only  fair  to  state  that  a  con- 
siderable number  of  the  fatalities  reported  on  the 
Continent  have  been  described  as  cases  of  death 
'  following  the  administration  of  salvarsan,'  which 
would  have  been  more  justly  recorded  as  cases  of 
death  '  occurring  in  spite  of  the  administration  of  sal- 
varsan.' Gibbard  and  Harrison  have  not  met  one  case 
in  over  1,000  injections  that  has  given  rise  to  anxiety. 

In  the  very  large  number  of  cases  treated  at  the 
London  Lock  Hospitals  two  deaths  have  followed 
treatment.  In  one,  no  error  of  technique  or  any 
cause  other  than  the  toxicity  of  the  fluid  injected  could 
be  found.  The  post-mortem  examination  showed  the 
changes  characteristic  of  toxaemia.  The  symptoms 
did  not  develop  until  three  days  after  the  second  dose. 
Degenerative  changes  were  found  in  the  liver,  and 
possibly  these  changes  were  induced  by  the  salvarsan, 
and  were  the  cause  of  the  toxic  symptoms.  The 
second  death  was  from  pulmonary  embolism,  resulting 
from  the  shifting  of  a  clot  from  a  vein  inflamed  above 
the  point  of  injection.  The  emboHsm  occurred  three 
days  after  injection. 

The  author,  in  a  considerable  personal  experience, 
has  met  no  case  giving  rise  to  apprehension,  with  the 
exception  of  two  cases  of  phlebitis,  one  of  slight 
transient  albuminuria,  and  one  of  syncope.     This  last 


TREATMENT  147 

case  occurred  in  a  patient  that  had  not  been  properly 
prepared  by  starving  and  purging. 

The  author  is  of  the  opinion  that  salvarsan  given  in 
the  present  dosage  is  practically  non-toxic,  and  that 
most,  if  not  all,  of  the  few  fatal  cases  recorded  are 
due  to  some  accident,  such  as  decomposition  of  the 
drug  owing  to  a  flaw  in  the  glass  ampule,  so  that  the 
vacuum  is  destroyed,  or  to  error  in  technique. 

Blindness. — Cases  of  blindness  have  been  recorded 
in  lay  journals  on  the  Continent ;  but  Ehrlich  cate- 
gorically states  that  no  case  has  been  reported  to  him, 
and  that,  despite  penetrating  research,  it  has  not  been 
possible  for  him  to  run  one  of  these  rumoured  cases 
to  earth.  In  medical  literature  the  danger  has  been 
constantly  hinted  at,  but  the  author  has  been  unable 
to  find  any  authenticated  case  of  actual  loss  of  sight 
following  treatment  by  salvarsan. 

On  the  other  hand,  many  observers  have  published 
cases  of  optic  neuritis  which  have  been  definitely 
improved  by  the  exhibition  of  salvarsan. 

Phlebitis  sometimes  occurs  in  the  vein  receiving 
the  injection.  If  this  sequel  arises,  the  arm  must  be 
kept  at  rest  and  the  limb  fomented  with  lead  and 
opium  lotion.  The  author  knows  of  one  case  in 
which  death  occurred  from  pulmonary  embolism 
caused  by  the  shifting  of  a  clot  from  a  vein  in  which 
phlebitis  had  occurred  as  a  result  of  the  injection. 

Nephritis. — Transient  albuminuria  has  been  observed 
in  several  cases,  and  a  very  few  cases  of  severe  and 
acute  nephritis  have  been  recorded  in  the  literature. 
A  few  cases  of  suppression  and  retention  of  urine  have 
also  been  reported. 


148  SYPHILIS  AND  PARASYPHILIS 

After-Effects. 

Pain  in  intravenous  injections  should,  with  correct 
technique,  be  limited  to  the  momentary  discomfort 
caused  by  entrance  of  the  needle.  Occasionally 
painful  local  infiltration  has  been  noted,  but  should  be 
regarded  purely  as  occasioned  by  faulty  technique,  by 
which  some  of  the  salvarsan  solution  escapes  into  the 
tissues  around  the  vein  and  there  sets  up  an  aseptic 
inflammation. 

Salvarsan  Fever  and  Saline  Fever.  — As  has 
been  pointed  out,  the  intravenous  injections  of  sal- 
varsan are  sometimes  followed  by  a  rise  in  temperature, 
sometimes  reaching  102°  F.,  and  occasionally  as  high 
as  105°  F.  This  rise  in  temperature  may  be  accom- 
panied by  rigors,  vomiting,  headache,  and  pains  in  the 
back.  The  onset  of  the  symptoms  usually  occurs 
from  half  an  hour  to  two  hours  after  the  injection. 
The  symptoms  usually  subside  in  a  few  hours. 

Wechselmann  has  suggested  that  these  symptoms 
might  be  caused  by  contamination  of  the  saline  solution, 
and  not  be  due  to  the  salvarsan,  and  Gibbard  and 
Harrison,  Macintosh  and  Fildes,  and  Holt  and  Pen- 
fold,  working  independently,  have  all  come  to  the 
conclusion  that  in  many  cases  it  is  the  saline  solution 
and  not  the  salvarsan  that  is  the  cause  of  "  salvarsan 
fever.' 

Gross  contamination  with  living  organisms  is  not 
the  only  cause,  for  the  fever  may  be  produced  if  the 
saline  solution  is  autoclaved  just  before  use,  so  that 
all  the  organisms  are  killed. 

The  question  has  not  been  definitely  settled  as  to 


TREATMENT  149 

whether  the  toxic  symptoms  are  produced  by  the 
dead  bodies  of  the  bacteria  acting  as  a  poisonous 
foreign  albumin,  or  by  thermo-stable  exotoxins  pro- 
duced in  the  saline  as  the  result  of  bacterial  action. 
The  results  of  numerous  experiments,  however,  make 
it  clear  that,  if  the  salt  solution  is  only  prepared 
immediately  before  use,  is  made  with  freshly  distilled 
water,  and  is  autoclaved  directly  it  is  mixed,  these 
toxic  symptoms  will  only  occur  in  cases  of  florid 
syphilis. 

Macintosh  and  Fildes  point  out  that  the  rigors  and 
toxic  symptoms,  which  occur  in  secondary  syphilis, 
must  be  different  in  origin  from  those  occurring  in 
other  forms  of  syphilis,  because  they  continue  in  spite 
of  the  use  of  microbe-free  saline  solution.  These 
authors  also  state  that  the  toxic  symptoms  which 
occur  in  secondary  syphilis,  and  are  uninfluenced  by 
the  careful  preparation  of  the  saline,  occur  later  than 
the  saline  rigors,  the  temperature  seldom  starting  to 
rise  for  three  or  four  hours. 

Schreiber  suggests  that  fever  in  secondary  syphilis 
is  the  result  of  the  liberation  of  large  quantities  of  endo- 
toxins from  the  destroyed  spirochaetae,  and  this  view 
the  author  shares. 

In  order  to  eliminate  the  risk  of  saline  fever — 

1.  Freshly  distilled  water  should  be  used. 

2.  Pure  sodium  chloride. 

3.  The  salt  should  be  added  to  the  distilled  water 
and  filtered,  and  the  filtered  solution  should  be  auto- 
claved immediately  before  use. 

The  author,  with  an  experience  extending  over 
nearly  two  years,  has  not  met  with  rigors  in  more  than 


I50  SYPHILIS  AND  PARASYPHILIS 

5  per  cent,  of  cases,  vomiting  has  been  very  occasional, 
and  the  temperature  has  rarely  been  raised  above 
1 00°  F.  except  in  a  few  cases  of  florid  syphilis. 

Vomiting,  when  it  occurs,  usually  takes  place  from 
half  an  hour  to  three  hours  after  the  injection. 

Rigors  are  rare,  but  occasionally  occur  from  half  an 
hour  to  four  hours  after  injection. 

Headache  and  pains  in  the  back  are  met  with  in 
a  considerable  percentage  of  cases. 

Diarrhoea  and  constipation  are  occasional  effects 
of  treatment,  the  former  occurring  soon  after  the  injec- 
tion, and  the  latter  after  an  interval  of  a  few  days. 
Neither  condition  is,  as  a  rule,  of  serious  import. 

Both  jaundice  and  rectal  tenesmus  occur  as  very 
rare  sequels. 

A  temporary  exacerbation  of  an  existing  skin 
eruption  (the  Jarisch-Herxheimer  reaction)  is  not 
infrequently  seen.  Two  hours  or  so  after  the  injection 
cutaneous  lesions  become  deeper  in  colour  and  more 
diffuse.  This  effect  reaches  its  highest  point  in  about 
twelve  hours  and  then  gradually  disappears  in  the 
course  of  the  next  few  days. 

A  sense  of  cardiac  oppression,  sometimes  going  on 
to  syncope,  and  throbbing  in  the  head  have  been 
described  as  occurring  at  the  time  of  intravenous 
injection,  but  the  author  has  not  observed  these  symp- 
toms in  properly  prepared  cases.  Purgation  and 
abstinence  from  food  before  treatment  should  be 
enforced  in  each  case,  and  this  preparation  of  the 
patient,  combined  with  slow  injection  of  the  drug,  can 
be  relied  upon  to  obviate  the  occurrence  of  these 
symptoms. 


TREATMENT  151 

The  effect  on  the  general  health  is  strikingly  benefi- 
cial in  the  vast  majority  of  cases.  There  is  at  first  a 
slight  depression,  with  loss  of  appetite,  lasting  twelve 
to  forty-eight  hours,  after  which  rapid  improvement  is 
usually  seen.  In  most  cases  there  is  a  very  definite 
gain  of  weight,  varying  from  a  few  pounds  up  to  twenty 
or  more  in  a  month. 

The  composition  of  the  blood  is  modified  by  salvar- 
san,  but  the  changes  observed  are  not  constant. 
Normally  there  is  a  definite  increase  in  the  number  of 
red  corpuscles,  and  also  in  the  amount  of  haemoglobin. 
Levy-Bing  and  Duroeux,  however,  quote  a  case  in 
which  a  fall  of  red  cells,  amounting  to  1,400,000  is 
recorded.  Leucocytosis  is  the  rule.  It  may  be  as 
high  as  30,000,  but  a  more  usual  count  is  17,000.  The 
increase  occurs  chiefly  in  neutrophil  cells,  but  eosino- 
philia  has  occasionally  been  observed.  Sabrazes  has 
worked  out  in  minute  detail  the  various  changes  occur- 
ring in  the  blood  after  treatment.  Clinically,  very 
striking  improvement  is  seen  in  cases  of  syphilitic 
anaemia,  the  pallor  and  sallowness  disappearing  in  the 
course  of  a  week  or  two. 

Relapses. 

Several  cases  of  chancre  successfully  treated,  in  so 
far  as  complete  resolution  had  resulted  in  a  week  or  so, 
have  subsequently  developed  typical  secondaries. 
Most  of  these  have  cleared  up  in  a  few  days  after  a 
second  injection.  Many  relapses  have  also  occurred  in 
cases  treated  in  the  secondary  and  tertiary  stages  of 
the  disease,  and  in  these  also  reinjection  has,  in  the 


152  SYPHILIS  AND  PARASYPHILIS 

majority  of  instances,  caused  disappearance  of  the  fresh 
lesions. 

Various  causes  have  been  put  forward  to  explain 
the  incidence  of  relapse  which  may  be  summarized 
as  follows : 

1.  That  the  dose  of  salvarsan  has  been  insufficient 
to  kill  the  spirochaetcE. 

In  this  connection  it  is  interesting  to  recall  the 
experiments  of  Hata  upon  animals,  which  showed  that 
half  a  curative  dose  was  ineffective.  Moreover,  Duhot 
attributes  his  success  to  the  large  doses  (maximum 
I  •!  gramme)  which  he  has  invariably  employed. 

2.  That  some  of  the  spirochsetae  lie  embedded  in 
thrombi  or  protected  by  dense  inflammatory  tissue,  and 
only  escape  after  the  complete  excretion  of  the  drug. 

Reinduration  of  a  chancre  might  be  explained  on 
this  hypothesis,  and  excision  of  the  chancre  at  the  time 
of  the  injection,  as  advocated  by  many  authors,  would 
thus  appear  to  rest  on  a  rational  basis.  The  simul- 
taneous administration  of  fibrolysin  or  reinjection  with 
salvarsan  at  an  early  date  has  also  been  recommended 
with  the  same  object  in  view  ;  in  the  latter  case  on  the 
supposition  that  the  first  dose,  although  unable  to  reach 
the  '  protected '  spirochsetae,  yet  promotes  sufficiently 
extensive  tissue  reaction  to  enable  the  second  to 
achieve  this  purpose. 

3.  That  in  certain  cases  some  or  all  the  spirochaetse 
are  resistant  to  salvarsan. 

We  know  that  in  a  few  rare  instances  spirochsetae 
are  resistant  to  mercury,  and  it  is  conceivable  that  an 
arsenic-fast  strain  is  occasionally  met  with,  although 
Ehrlich  strongly  opposes  this  view. 


TREATMENT  153 

4.  That  some  spirochaetae,  which  are  not  originally 
arsenic-fast,  become  so  after  the  administration  of  a 
dose  insufficient  to  kill  them. 

This  hypothesis  would  explain  those  cases  which 
have  relapsed  owing  to  an  insuflicient  dosage  after  an 
apparently  successful  treatment,  and  have  then  failed 
to  react  to  a  second  injection. 

Contra- Indications. 

The  contra-indications  for  treatment  with  salvarsan 
are  few.  The  remedy  is  very  well  tolerated  by  tuber- 
culous persons  in  all  stages.  Optic  atrophy  and 
diabetes  were  till  recently  considered  contra-indications, 
but  most  authorities  consider  that  salvarsan  is  harmless 
in  these  conditions. 

Herxheimer  considers  lesions  of  the  heart,  fcetid 
bronchitis,  and  non-syphilitic  disturbances  of  the  optic 
nerves  to  be  contra-indications.  Great  caution  is 
required  with  subjects  exhibiting  haemorrhagic  ten- 
dency. Arsenic  exerts  a  toxic  effect  upon  the  walls 
of  arterioles  and  capillaries,  and  the  drug  should  not 
be  given  in  advanced  disease  of  the  heart  or  arteries, 
but  small  thoracic  aneurisms  have  been  treated  by 
Wechselmann  without  any  injurious  effect.  McDonagh 
considers  bulbar  paralysis  a  contra-indication.  He 
also  recommends  that  .care  should  be  exercised  in 
cases  complicated  by  jaundice. 

It  is  generally  conceded  that  cases  of  nephritis 
which  are  not  of  syphilitic  origin  should  not  be  sub- 
jected to  the  treatment,  unless  albuminuria  is  of  sHght 
degree. 


154  SYPHILIS  AND  PARASYPHILIS 

Treatment  in  cases  of  intracranial  gumma  must  be 
regarded  as  fraught  with  danger,  and  advanced  de- 
generation of  the  central  nervous  system  or  cerebral 
haemorrhage  are  considered  a  contra-indication  by  the 
majority  of  observers. 

Conclusions. 

Ehrlich's  idea  of  therapia  stevilisans  magna — that  is  to 
say,  complete  and  lasting  cure  of  the  disease  by  a 
single  dose  of  the  drug — has  undoubtedly  been  realized 
in  relapsing  fever.  In  the  case  of  syphilis  the  ques- 
tion must  be  held  to  be  '  not  proven '  at  the  present 
date.  Many  years  must  necessarily  elapse  before  one 
can  arrive  at  a  definite  decision  when  dealing  with  a 
disease  which  may  lie  dormant  for  as  long  a  period  as 
twenty  years,  and  then  recrudesce  spontaneously. 

Salvarsan  has  a  striking  and  rapid  effect  on  the 
clinical  manifestations  of  syphilis  ;  this  is  particularly 
the  case  in  malignant  syphilis  when  ulcerative  lesions 
of  skin  and  mucous  membranes  are  present. 

Pain  disappears  as  if  by  magic. 

Salvarsan,  when  it  does  produce  an  alteration  of  the 
serum  reaction,  does  so  more  rapidly  than  mercury. 
On  the  other  hand,  in  the  present  state  of  our  know- 
ledge, it  would  appear  that  the  percentage  of  negative 
results  after  one  or  two  injections  is  lower  than  that 
observed  after  a  year's  course  of  efficient  mercurial 
treatment. 

Spirochaetai  disappear  in  two  or  three  days  from  all 
superficial  lesions,  and  the  period  of  infectivity  is  thus 
reduced  to  a  minimum — a  fact  of  great  sociological 
importance,  especially  in  military  stations. 


TREATMENT  155 

The  danger  of  death,  of  bhndness,  or  other  grave 
lesion,  is  so  sHght  in  carefully  selected  cases  that  there 
is  no  justification  for  withholding  salvarsan. 

The  best  results  are  obtained  with  administration 
by  the  intravenous  route,  but  this  should  only  be 
undertaken  by  workers  who  are  skilled  in  the 
technique. 

Neo-Salvarsan,  which  is  the  name  that  has  been 
given  to  a  neutral  preparation  of  the  drug,  is  a  recent 
modification.  It  is  more  easily  soluble  than  salvarsan, 
and  does  not  require  neutralizing  with  sodium  hydrate. 
It  is  said  to  be  less  toxic  than  salvarsan,  but  as  the 
toxicity  of  salvarsan  is  minimal,  the  advantages  of 
the  new  salt  consist  chiefly  in  simplicity  in  prepara- 
tion. 0-6  gramme  can  be  mixed  with  250  c.c.  of 
sterile  distilled  water,  and  injected  without  any  further 
preparation.  This  simplicity  of  preparation,  however, 
is  of  some  importance,  as  it  obviates  the  possibility  of 
adding  an  excess  of  alkali,  which  excess  might  alone 
produce  toxic  symptoms.  The  question  as  to  the  rela- 
tive therapeutic  value  of  salvarsan  and  neo-salvarsan 
has  yet  to  be  proved. 

MERCURY 

As  will  be  seen  in  the  next  chapter,  the  administra- 
tion of  mercury  by  the  mouth  does  not  appear  to  be 
nearly  as  effective  as  when  given  intramuscularly  in 
the  form  of  insoluble  preparations.  The  administra- 
tion of  mercury  by  suppositories  appears  to  have  little 
to  recommend  it,  but  mercurial  inunctions  are  very 
potent.    There  is,  however,  but  little  to  choose  between 


156  SYPHILIS  AND  PARASYPHILIS 

mercurial  inunctions  and  intramuscular  injections,  any 
slight  superiority  in  potency  in  the  former  being  dis- 
counted by  the  obvious  social  inconvenience  of  this 
method  of  treatment  in  the  majority  of  cases.  The 
only  form  of  mercurial  treatment  detailed  here,  there- 
fore, will  be  intramuscular  injections. 

Site  of  Injection. — The  most  convenient  sites  for 
the  injections  are — 

1.  An  area  at   the  junction  of  the  middle  and 

posterior  third  of  a  line  from  the  anterior 
superior  iliac  spine  to  the  great  trochanter. 

2.  The  upper  and  external  quadrant  of  the  gluteal 

region. 
The  site  of  puncture  should  be  cleaned  with  ether  and 
alcohol,   and   sterilized  with  a  saturated   solution  of 
iodine  in  chloroform. 

Calomel  cream  is  probably  one  of  the  most  efficacious 
preparations,  and  may  be  used  of  such  a  strength  that 
5  minims  of  the  cream  contain  0*75  grains  of  calomel, 
10  minims  being  given  as  a  dose  for  an  adult. 

Mercurial  cream  can  be  used  of  such  a  strength 
that  5  minims  contain  i  grain  of  metallic  mercury, 
10  minims  being  given  as  a  dose. 

A  course  of  mercurial  injections  usually  consists  of 
twelve  doses,  the  first  four  of  which  may  be  calomel 
cream,  and  the  last  eight  mercurial  cream. 

A  detailed  account  of  mercurial  treatment  of  syphilis 
lies  outside  the  scope  of  this  work,  and  will  be  found 
in  any  textbook  dealing  with  syphilis. 

As  regards  parasyphilis,  Dr.  Risien  Russell  is  fully 
convinced  of  the  efficacy  of  mercury  administered  by 
inunction  or  injection  in  tabes.,  and  considers  that  no 


TREATMENT  157 

patient  in  the  early  stages  of  this  disease  should  be 
allowed  to  go  untreated.  He  has  obtained  no  im- 
provement in  general  paralysis. 

This  appears  to  be  the  opinion  of  the  majority  of 
neurologists. 

A  convenient  syringe  and  needle  for  intramuscular 
injection  are  shown  in  Fig.  22. 


Fig.  22. — Syringe  and  Needle  for  Administration  of  Intra- 
muscular Injections  of  Mercurial  Cream. 


COMBINED  SALVARSAN  AND  MERCURIAL 
TREATMENT 

Neisser  has  given  it  as  his  opinion  that  in  order  to 
obtain  a  curative  result  it  must  be  better  to  attack  the 
enemy  from  two  sides  rather  than  from  one  side  alone. 
He  states  that  it  is  beyond  all  doubt  that  a  surer, 
more  brilliant,  and  more  lasting  curative  effect  will 
follow  if  we  combine  the  two  remedies — salvarsan 
and  mercury. 

The  author  suggests  that  the  combined  treatment 
should  be  given  as  a  matter  of  routine  in  all  cases, 
and  in  the  following  way  : 

I.  The  intravenous  injection  of  o'6  gramme  of 
salvarsan  to  be  repeated  in  forty-eight  hours 
by  a  second  dose,  providing  that  the  tempera- 


158  SYPHILIS  AND  PARASYPHILIS 

ture  has  been  normal  for  twenty-four  hours, 
and  that  no  nephritis  has  developed. 

2.  This  is  followed  by  twelve   mercurial   intra- 

muscular injections,  the  first  four  consisting 
of  calomel  cream,  and  the  last  eight  mercurial 
cream. 

3.  Two  more  intravenous  injections  of  salvarsan 

are  now  given.  If  there  is  any  temperature 
on  the  second  day  after  the  first  intravenous 
injection  of  salvarsan,  the  second  dose  should 
not  be  administered,  but  should  be  postponed 
until  the  temperature  has  been  normal  for 
twenty- four  hours. 

4.  The  Wassermann  reaction  should  be  examined 

two  months  after  the  last  dose  of  salvarsan, 
and,  if  positive,  a  second  course  of  mercurial 
injections  should  be  given.  If  the  reaction 
is  negative,  immediate  further  treatment  is 
not  indicated. 

5.  The  Wassermann  reaction  should  be  examined 

every  three  months  for  two  years,  and  occa- 
sionally afterwards,  and  a  further  course  of 
treatment  undertaken  should  the  reaction 
return  to  positive. 


CHAPTER  XIV 

EFFECT  OF  TREATMENT  ON  THE 
WASSERMANN  REACTION 

MERCURY 

The  effect  of  mercurial  treatment  is  usually  clearly 
seen,  and  depends  on  the  time  in  the  history  of  the  infec- 
tion that  treatment  began,  and  the  length  and  nature  of 
the  treatment.  Neisser  has  observed  that  the  earlier  in 
the  course  of  the  disease  that  treatment  is  commenced, 
the  more  probability  there  is  that  a  negative  result  will 
be  obtained  after  a  course  of  treatment.  Where  treat- 
ment began  as  soon  as  possible  after  the  primary 
lesion  had  appeared,  75  per  cent,  of  negative  reactions 
were  subsequently  obtained,  whereas,  if  treatment  has 
been  delayed  for  six  months,  only  33  per  cent,  of 
negatives  were  obtained  after  treatment. 

Of  late  latent  cases — that  is,  cases  several  years  after 
infection  in  which  there  are  no  symptoms — he  found 
that  the  early  treated  cases  gave  negative  results  in 
80  per  cent,  of  cases,  and  the  late  treated  cases  in  only 
58  per  cent.  Purckhauer  reports  the  result  of  treat- 
ment on  165  cases  at  different  stages  of  the  infection, 
all  of  which  were  positive  before  treatment.  Of 
116  primary  and  secondary  cases,  75  per  cent,  became 

159 


i6o  SYPHILIS  AND  PARASYPHILIS 

negative  ;  of  15  late  latent  cases,  4  became  negative; 
and  of  18  tertiary  cases  only  2  became  negative.  Of 
4  cerebral  cases  only  i  became  negative  after  treat- 
ment. The  longer  infection  has  persisted,  the  more 
stable  the  positive  reaction  seems  to  become,  and  the 
greater  difficulty  there  is  in  inducing  a  negative  re- 
action after  treatment.  In  some  late  tertiary  and  para- 
syphilitic  conditions  a  negative  reaction  is  never 
produced  even  by  the  most  rigorous  mercurial 
treatment. 

Occasionally  a  case  is  diagnosed  as  syphilis  and 
gives  a  negative  reaction,  and  yet  after  being  on 
mercury  for  a  while  positive  reaction  is  obtained. 
This  probably  is  due  to  the  fact  that  the  mercury 
destroys  numbers  of  spirochaetae,  whose  endotoxins 
are  then  liberated,  and  stimulate  the  production  of  the 
complement-fixing  substance.  If  5  per  cent,  of  com- 
plement is  fixed,  the  case  must  be  reported  as  positive, 
and  15  per  cent,  of  complement  is  only  used  in  order 
to  obtain  a  rough  idea  of  progress  under  treatment. 
Active  syphilis  will  generally  deviate  10  to  15  per  cent, 
of  complement,  but  as  the  infection  becomes  less  the 
amount  of  complement  deviated  also  becomes  less.  In 
this  way  it  is  possible  to  make  a  rough  quantitative 
measurement  of  the  amount  of  complement  fixed  and 
of  the  progress  made  under  treatment,  even  though  the 
case  must  still  be  returned  as  '  positive.' 

Using  this  method,  the  author  has  compared  the 
therapeutic  value  of  some  of  the  different  methods  of 
administering  mercury. 

The  tables  in  this  chapter  show  the  results  that 
were  obtained  with  the  various  treatments  as  far  as 


TREATMENT  AND  WASSERMANN  REACTION     i6i 

the   Wassermann    reaction  is   concerned.     Complete 
inhibition   of  haemolysis  is  indicated  by  the  sign    +  ; 
partial  inhibition,  by  the  sign  ±  ;  and  complete  haemo- 
lysis by  the  sign    - .     Complete  inhibition  of  haemo- 
lysis with   both   amounts  of  complement  the  author 
calls    '  strongly    positive,'   while    '  positive '    denotes 
that,   though  there   is  complete   inhibition   with   the 
smaller  amount   of   complement,  there  is  haemolysis 
with  the  larger  amount.     If  the  haemolysis  with  the 
smaller  amount  of   complement    is  partial  only,  the 
result  is  recorded  as   'doubtful'     All   the  cases   re- 
corded were  '  strongly  positive '  before  the  treatment 
was  commenced,  and  therefore  *  positive,'  '  doubtful,' 
and  '  negative,'  all  show  influence  of  treatment  in  a 
roughly  quantitative  manner.     Very  frequently  cases 
are  met  with  that  begin  at  '  strongly  positive,'  pass 
through   the  *  positive '    and    '  doubtful '    stages,   and 
end  at  '  negative.' 


Table  V.  (Harrison). — Effect  of  Treatment  with 
Intramuscular  Injection. 


o 

0  u 

nal 
lent. 

nt. 
some 
of 
nt. 

+ 

+ 

-a  ^ 

■sE 

0    rj    t! 

■n't:  V 

0  £?ti  S 

"rt 

c 
<u 

S  <3 

Addi 
Compl 

Per 

Showir 

Effe 

Treat 

0 

H 

u 

u 
Ph 

After  I  course 

(of  3  months) 

55 

17 

29 

690 

46 

836 

After  2  courses 

49 

24 

14 

51 -o 

38 

77'5 

>>          3              5> 

42 

8 

19 

809 

27 

64  5 

n       4         M 

30 

3 

14 

90*0 

17 

.56-5 

>>          5              M 

34 

4 

13 

88-2 

17 

50-0 

,,     6       „ 

26 

3 

6 

S8-4 

9 

34-6 

II 


l62 


SYPHILIS  AND  PARASYPHILIS 


Pills  and  suppositories  seem  to  be  of  the  slowest 
and  least  efficient  forms  of  treatment,  and  inunctions 
and  intramuscular  injections  of  insoluble  compounds 
the  quickest  and  most  efficient.  Harrison  has  shown 
clearly  the  influence  of  only  short  treatment,  for, 
although  the  percentage  of  *  positives'  remains  high, 
some  effect  of  treatment  is  recorded  in  69  per  cent,  of 
cases  after  only  one  course  (see  Table  V.). 

With  pills,  on  the  other  hand,  95  per  cent,  of  cases 
treated  for  six  months  or  under  are  positive,  and 
only  5  per  cent,  show  any  effect  of  treatment  (see 
Table  VI.). 

Table  VI. — Pills  (122  Tests). 

Wassermann  Reaction  with  less  than  Six  Months'  Treat- 
ment in  45  Cases. 


Complement,  per  cent. 
Wassermann  reaction  . . 

Number  of  cases 
Percentage  of  cases 

5      15 

4-       4- 

Strongly 

positive. 

41 
91 

5      15 

4-       - 

Positive. 
2 

4 

5      15 
±      - 

Doubtful. 

I 

2-5 

5      15 

Negative. 

I 

2-5 

Wassermann  Reaction  with  Six  to  Twelve  Months'  Treat- 
ment in  33  Cases. 


Complement,  per  cent. 

5      15 

5 

15 

5 

15 

5 

15 

Wassermann  reaction  . . 

4-      + 

4- 

4- 

Number  of  cases 

20 

^ 

3 

7 

Percentage  of  cases 

61 

9 

9 

21 

TREATMENT  AND   WASSERMANN  REACTION     1G3 


Wassermann  Reaction  ivith  Treatment  for  Eighteen  Months 
or  Over  in  44  Cases. 


Complement,  per  cent. 
Wassermann  reaction  . . 
Number  of  cases 
Percentage  of  cases 

5      15 

^■     + 

8 

18 

5      15 

+      - 

5 
II 

5      15 
± 

10 
22 

5      15 

21 

48 

When  the  inunction  method  was  employed,  after 
three  months'  treatment,  only  i6-6  per  cent,  remained 
positive.  Daily  inunction  is  obviously  an  inconvenient 
method  of  treatment,  and  all  skins  do  not  tolerate  this 
method,  but  otherwise  inunction  would  seem  by  this 
too  short  series  to  be  the  most  satisfactory  form  of 
administration  of  mercury.  The  author  has  had  but 
little  opportunity  of  investigating  the  effect  on  the 
reaction  of  treatment  by  inunction  or  suppositories,  but 
the  short  series  examined  have  been  recorded  in 
Tables  VII.  and  VIII. 


Table  VII. — Suppositories  (33  Cases). 
Treatment  for  Six  Months  and  Under, 


Complement,  per  cent. 
Wassermann  reaction  . . 
Number  of  cases 
Percentage  of  cases 

5      15 
+      + 

20 

61 

5      15 

+      - 

6 

18 

5      15 
+      - 

4 
12 

5      15 

3 
9 

164 


SYPHILIS  AND  PARASYPHILIS 


Table  VIII. — Inunction  (26  Cases). 
Treatment  of  Two  to  Three  Months. 


Complement,  per  cent. 

5 

15 

5      15 

5 

15 

5      15 

Wassermann  reaction  . . 

-H 

+ 

+      - 

+ 

- 

-       - 

Number  of  cases 

3 

10 

3 

10 

Percentage  of  cases 

Hi 

384 

Hi 

38^ 

Table  IX. — Calomel  Intramuscular  Injections 
(109  Tests). 

Wassermann  Reaction  after  One  Course  of  Twelve  Injections 

in  54  Cases. 


Complement,  per  cent. 

5      15 

5      15 

5 

15 

5 

15 

Wassermann  reaction  . . 

+      + 

+ 

+ 

— 

- 

- 

Number  of  cases 

27 

13 

5 

9 

Percentage  of  cases 

50 

24 

9 

16 

Wassermann  Reaction  after  Two  Courses  in  35  Cases. 


Complement,  per  cent. 
Wassermann  reaction  . . 
Number  of  cases 
Percentage  of  cases 

5      15 

4-       4- 
II 

31 

5      15 

4-       - 

7 
20 

5      15 
±      - 

4 
II 

5      15 

13 

37 

Wassermann  Reaction  after  Three  Courses  in  20  Cases. 


Complement,  per  cent, 
Wassermann  reaction  . , 
Number  of  cases 
Percentage  of  cases 

5      T-5 

4-       4- 

2 

10 

5      15 

4-      - 

2 

10 

5      15 
±      - 

0 

0 

5      15 

16 
80 

TREATMENT  AND   WASSERMANN  REACTION     165 

Intramuscular  injection,  however,  appears  almost, 
if  not  quite,  as  potent  as  inunction,  and  to  be  undeni- 
ably superior  to  pill  treatment.  That  it  is  not  the 
presence  of  the  mercury  itself  in  the  blood  that  produces 
a  negative  reaction,  was  shown  by  Bauer,  who 
demonstrated  that  a  strong  positive  can  be  obtained 
when  the  mercury  excretion  in  the  urine  is  most 
marked,  and  that  a  negative  reaction  may  be  present 
when  the  mercury  excreted  in  the  urine  is  weak  or 
absent.  He  showed  that  a  previous  negative  reaction 
may  become  positive  in  spite  of  a  large  quantity  of 
mercury  in  the  blood,  and  that  a  reaction  which  has 
become  negative  under  treatment  can  become  positive 
in  spite  of  mercury  persisting  in  the  urine. 

Nearly  all  authorities,  both  Continental  and  Ameri- 
can, agree  that  in  the  future  treatment,  whether  by 
mercury  or  salvarsan,  must  be  regulated  by  the 
Wassermann  reaction.  A  solitary  negative  reaction 
obtained  with  the  serum  of  a  patient  undergoing 
mercurial  or  salvarsan  treatment  means  little  but  that 
the  patient  is  reacting  to  the  treatment.  A  sevies  of 
negative  results  taken  at  intervals  of  three  to  six 
months  after  ail  treatment  has  been  given  up  is  neces- 
sary before  the  patient  can  be  regarded  as  cured,  and  even 
then  until  another  twenty  years  have  passed  we  can- 
not be  absolutely  certain  that  the  disease  is  completely 
and  permanently  obliterated,  and  that  no  late  manifesta- 
tions will  ever  occur.  It  is  important  to  remember  that 
about  10  per  cent,  of  untreated  cases  of  syphilis  fail  to 
give  a  positive  reaction  at  the  first  examination,  and 
that  therefore  a  negative  reaction  only  gives  a  90  per 
cent,  probability  of    freedom    from   infection.     If,   in 


i66  SYPHILIS  AND  PARASYPHILIS 

recently  acquired  syphilis,  after  several  months'  treatment, 
the  reaction  still  remains  strongly  positive,  and  large 
doses  of  complement  are  still  fixed,  it  is  an  indication 
that  the  treatment  is  inefficient,  and  that  more  rigor- 
ous methods  should  be  adopted.  If,  however,  after 
each  course  of  treatment  a  smaller  amount  of  comple- 
ment is  fixed,  or  the  intervals  before  a  positive  reaction 
returns  become  longer  and  longer,  we  may  conclude 
that  the  treatment  is  satisfactory,  and  that  there  is  no 
necessity  to  increase  the  dose. 

The  author's  further  experience  confirms  his  original 
conclusions,  that  inunction  and  intramuscular  injection 
are  by  far  the  most  rapid  methods  of  producing  a  nega- 
tive Wassermann  reaction  by  mercurial  treatment. 

SALVARSAN 

Salvarsan  usually  produces  a  negative  reaction 
more  quickly  than  mercury,  but  apparently  the 
percentage  of  negative  results  after  one  or  two  intra- 
venous injections  of  the  doses  employed  (0-4  gramme) 
is  lower  than  that  observed  after  a  year's  course  of 
efficient  mercurial  treatment.  The  following  results 
were  obtained  in  fifty  cases  where  the  reaction  could 
be  followed  for  several  months  : 

Changed  from  positive  to  negative  . .  •  •  31 

Reduced  quantity  of  complement  fixed  . .  . .  7 

Reaction  unchanged     . .              . .  . .  . .  6 

Relapsed  from  negative  to  positive  . .  . .  6 

Of  the  total  50  cases  treated  with  salvarsan  and 
examined  four  weeks  and  over  after  treatment,  30 
(60  per  cent.)  became  negative,  while,  when  examined 
under  four  weeks,  only  9  (18  per  cent.)  were  negative. 


TREATMENT  AND  WASSERMANN  REACTION     167 

The  results  obtained  which  give  42  per  cent,  nega- 
tive after  intramuscular  injections,  52  per  cent,  after 
one  intravenous  injection,  and  74  per  cent,  after  two 
intravenous  injections,  seem  to  indicate  that  the  intra- 
venous route  is  the  best,  and  that  at  least  two  injections 
should  be  given  (see  Table  X.). 

The  dose  given  in  the  great  majority  of  intravenous 
cases  was  0*4  gramme,  and  now  that  we  know  that 
usually  larger  doses  can  safely  be  employed,  we  may 
hope  to  obtain  a  higher  percentage  of  negative  results 
and  a  lower  percentage  of  relapses. 


Table  X. — Injections  of  Salvarsan  (200  Tests). 

Wassevmann  Reaction  Four  Weeks  after  One  Intravenous 
Injection  in  21  Cases. 


Complement,  per  cent. 

5 

15 

5      15 

5      15 

5      15 

Wassermann  reaction  . . 

+ 

+ 

+      - 

+      - 

Number  of  cases 

3 

5 

2 

II 

Percentage  of  cases 

14 

24 

10 

52 

Wassermann  Reaction  Four  to  Eight  Weeks  after  Two 
Intravenous  Injections  in  50  Cases. 


Complement,  per  cent. 

5 

15 

5 

15 

5 

15 

5      15 

Wassermann  reaction  . . 

+ 

+ 

+ 

-H 

Number  of  cases 

6 

^ 

4 

37 

Percentage  of  cases 

12 

6 

8 

74 

1 68 


SYPHILIS  AND  PARASYPHILIS 


Wassevmann  Reaction  Four  to  Eight  Weeks  after  Intra- 
muscular Injection  of  Salvarsan  in  12  Cases. 


Complement,  per  cent. 
Wassermann  reaction  . . 
Number  of  cases 
Percentage  of  cases 

5      15 

+      + 

5 

42 

5      15 

+      - 

I 
8 

5      15 
±      - 

I 

8 

5      15 

5* 
42 

Relapses. — Wassermann  Reaction  Six  to  Twelve  Months 
after  Two  ov  move  Intravenous  Injections  of  Salvarsan 
in  37  Cases  that  had  become  Negative  as  the  Result  of 
such  Treatment. 


Complement,  per  cent. 
Wassermann  reaction  . , 
Number  of  cases 
Percentage  of  cases 

5      15 

+      + 

2-0 
5-5 

5      15 

+     - 

3 

8 

5      15 
±      - 

20 

55 

5      15 

30 

81 

It  will  be  seen  from  Table  X.  that  over  70  per  cent,  of 
cases  treated  with  salvarsan  became  negative  in  from 
four  to  eight  weeks  after  the  second  intravenous 
injection,  and  that  80  per  cent,  of  these  negatives 
remained  negative  six  to  twelve  months  afterwards. 
Over  50  per  cent.,  therefore,  of  cases  that  before  treat- 
ment were  strongly  positive  became  negative,  and 
still  remained  so  when  examined  six  to  twelve 
months  after  treatment.  Of  course,  a  negative  re- 
action persisting  for  six  to  twelve  months  does  not 
necessarily  mean  permanent  cure,  but  it  is  at  least 
extremely  encouraging  that  there  is  no  pathological  evi- 
dence of  relapse  in  over  half  the  cases.  In  some  cases 
salvarsan,  even  in  repeated  doses  (sometimes  as  many 

*  Two  of  these  relapsed  to  positive  or  doubtful. 


TREATMENT  AND   WASSERMANN  REACTION     169 

as  six  have  been  given),  has  no  effect  whatever  on  the 
reaction.  The  author  is  inclined  to  think  that  cases 
that  are  going  to  relapse  will  show  evidence  of  such 
relapse  by  the  Wassermann  reaction  in  under  six 
months  in  the  great  majority  of  instances.  On 
comparing  Tables  VI.,  IX.,  and  X.,  it  will  be  seen 
that  only  48  per  cent,  of  cases  treated  with  pills 
become  negative  after  eighteen  months'  treatment, 
whereas  80  per  cent,  become  negative  after  three 
courses  (one  year's  treatment)  of  intramuscular  in- 
jections. How  many  of  these,  however,  would  remain 
negative  six  months  later  if  all  treatment  were  dis- 
continued it  is  impossible  to  say,  as  the  author  had 
not  opportunities  for  such  investigation.  At  the 
London  Lock  Hospitals  considerable  difficulty  is 
experienced  in  getting  patients  to  return  for  blood- 
examination  after  they  have  severed  their  connection 
with  the  hospital. 

Table  XI.  shows  the  periods  at  which  reactions 
became  negative  in  seven  cases  in  which  several 
examinations  have  been  made  over  the  period  of 
twelve  months. 

Table  XI. 


^ 

u   § 

Month. 

0  E 

1;  rt 

W  JJ 

I. 

2.        3. 

4- 

5- 

6.       7. 

8. 

Q. 

10. 

II. 

12. 

M.  15. 

H 
h  + 

— 

_ 

1 

S.  C. 

\-  + 

-    - 

+  - 

-    - 

-    _ 

C.  D. 

+  + 

-    - 

-  — 

-    _ 

E.  H. 

+  + 

-    - 

-    - 

-    - 

-    - 

-    - 

M.  L. 

f  + 

+  - 

f  + 

+   - 

-    - 

-    _ 

H.  S. 

f  + 

+   - 

f  ± 

±  - 

1-    — 

rl-  - 

-    - 

-    - 

A.  S. 

\-  + 

±  - 

±   - 

±   - 

~    ~ 

170 


SYPHILIS  AND  PARASYPHILIS 


Table  XII.  gives  the  results  obtained  in  the  seven 
cases  in  which  the  quantity  of  complement  -  fixing 
substance  was  reduced  by  salvarsan  treatment  although 
a  negative  reaction  was  not  obtained. 


Table  XII. — Incomplete  Results. 


^  c                                                        Month. 

Bef( 
Treatr 

2. 

3- 

4- 

5- 

6. 

±  - 
±  - 

+  - 

7- 

8. 

9- 

10. 

II. 

12. 

F.  H. 
M.  S. 
J.B. 
R.  C. 

w.  e. 

E.  H. 
A.  H. 

1 
+  -' 
+  +.+  + 

+  +1 

+  -  +   - 

+  -| 

+  +'+  + 

±  - 
+  + 

+  ± 
±  - 

±  - 

+  + 

-    - 

+  - 

+  - 

All  the  six  relapses  occurred  during  the  first  six 
months  following  treatment,  such  cases  that  were 
negative  six  months  after  treatment  still  being  negative 
after  twelve  months  (see  Table  XIII.). 

Table  XIII. — Relapses. 


Month. 

I.        2. 

3- 

4-        5- 

6. 

7.      s. 

9- 

10. 

ir. 

12. 

E.  D. 
N.  H. 
B.  L. 
E.  R. 
L.  W. 
L.  W. 

+  + 
+  + 
+  + 
+  + 
+  + 
+  + 

-  -'+  - 

-  -  +  ± 

4_ 

+  - 
+  - 
±  - 
+  - 

+  + 

+  + 

+  + 

^ 

TREATMENT  AND  WASSERMANN  REACTION     171 

If  rapidity  of  change  of  reaction  be  taken  as  a  test 
of  efficiency  of  treatment,  the  author  would  place 
salvarsan  first,  inunction  or  intramuscular  injection 
of  insoluble  mercury  compounds  second,  and  mercurial 
pills  and  suppositories  a  bad  third.  The  author  con- 
siders the  results  obtained  suggest  the  advisability  of 
combined  salvarsan  and  mercurial  treatment. 


CHAPTER  XV 

ANAPHYLAXIS  AND  SYPHILIS 

By  anaphylaxis  is  meant  a  condition  of  increased  sen- 
sitiveness to  any  antigen  as  the  result  of  inoculation 
with  such  antigen. 

It  is  therefore  the  opposite  of  immunity,  which  is  a 
state  of  decreased  sensitiveness  to  the  antigen. 

Anaphylactic  phenomena,  like  immunity  phenomena, 
are  the  result  of  an  antigen-antibody  reaction,  and  are 
strictly  specific  in  nature.  Thus  a  state  of  anaphylaxis 
to  any  given  antigen  can  only  be  produced  by  a  second 
inoculation  with  the  same  kind  of  antigen,  and  after  suffi- 
cient time  has  elapsed  to  permit  of  the  development 
of  the  corresponding  antibody. 

Although  the  phenomenon  is  the  result  of  a  specific 
antigen  -  antibody  reaction,  the  symptoms  of  acute 
anaphylaxis  are  similar  whatever  the  antigen  used 
may  be,  whether  serum,  organism,  toxin,  or  other 
foreign  proteid. 

Two  varieties  of  hypersensitiveness  to  serum  de- 
serve special  mention,  as  they  are  typical  of  ana- 
phylactic phenomena,  however  produced : 

I.  Arthus'  Phenomenon.  —  Arthus'  phenomenon 
appears  when  a  guinea-pig  receives  several  sub- 
cutaneous injections,  at  intervals  of  a  few  days,  of 
normal  horse  serum,  a  substance  which  in  itself  is 

172 


ANAPHYLAXIS  AND  SYPHILIS  173 

scarcely  more  toxic  than  normal  solution.  After  a 
few  such  inoculations  the  animal  becomes  hyper- 
sensitive, or  anaphylactized,  and  after  another  injection 
an  oedematous  mass,  an  aseptic  abscess,  or  an  area 
of  necrosis,  appears  at  the  site  of  a  new  inoculation, 
which  need  not  be  in  a  region  in  which  a  previous 
injection  has  been  made  ;  the  alteration  is  a  general, 
and  not  a  local  one.  After  several  of  these  injections 
the  animal  becomes  cachectic,  and  dies  after  several 
weeks. 

2.  Theobald  Smith's  Phenomenon.  —  Theobald 
Smith's  phenomenon  occurs  when  an  animal  has  been 
sensitized  by  a  very  small  injection  of  horse  serum, 
and  kept  for  a  fortnight  or  more.  If,  then,  a  second 
injection  of  a  larger  amount  of  the  same  serum  be 
made,  the  animal  develops  a  series  of  remarkable 
symptoms,  the  most  noteworthy  being  respiratory 
failure,  paralysis,  and  clonic  spasms.  Symptoms 
usually  appear  within  ten  minutes,  and  death  occurs 
within  an  hour.  Death  does  not  always  follow.  The 
less  sensitive  the  animal  the  later  the  development  of 
symptoms,  and  the  greater  the  chance  of  survival. 
The  process  evidently  affects  the  nervous  system  in 
a  very  special  way. 

Various  phenomena  that  sometimes  occur  during 
the  course  of  syphilitic  infection  may  perhaps  be  the 
result  of  a  state  of  anaphylaxis  to  the  toxin  produced 
by  the  SpirochcBta  pallida.     Thus — 

The  Jarisch  Herxheimer  Reaction  (the  tem- 
porary lighting-up  of  symptoms  very  occasionally 
produced  by  an  injection  of  salvarsan  or  by  a  large 
mercurial  inunction)  ; 


174  SYPHILIS  AND  PARASYPHILIS 

Salvarsan  Fever,  accompanied  by  rigors,  vomit- 
ing, headache,  diarrhoea,  etc.,  that  occasionally  occurs 
in  florid  syphilis  ; 

And  Justus'  Test,  in  which  a  fall  in  the  haemo- 
globin content  of  the  blood  follows  a  large  inunction 
or  injection  of  mercury  ; 

may  all  possibly  be  caused  by  a  state  of  anaphylaxis 
produced  by  the  setting  free  of  a  large  quantity  of 
specific  endotoxin  as  the  result  of  destruction  of  the 
spirochaetae. 

Of  the  very  few  deaths  following  the  administration 
of  salvarsan  that  cannot  be  explained  by  errors  in 
technique,  several  have  been  preceded  by  symptoms 
suggestively  similar,  in  the  author's  opinion,  to  those 
occurring  in  acute  anaphylaxis  of  the  Theobald  Smith 
type. 

Studies  in  anaphylaxis  by  numerous  observers  have 
shown  that  the  hypersensitiveness  to  the  foreign  pro- 
tein (antigen)  takes  some  time  to  develop,  and  does 
not  develop  at  all  if  the  inoculation  process  is  con- 
tinuous ;  in  other  words,  there  must  be  a  cessation  of 
inoculations  for  a  certain  period  of  time,  generally 
about  ten  to  fourteen  days,  before  the  anaphylactic 
phenomenon  develops,  and  the  continuance  of  the 
inoculations  at  regular  short  intervals  does  not  pro- 
duce anaphylaxis. 

NOGUCHFS   LUETIN    REACTION 

Noguchi  points  out  that  an  anaphylactic  condition 
is  more  likely  to  develop  in  those  patients  who  are 
infected  with  certain  organisms  which  remain  in  their 


ANAPHYLAXIS  AND  SYPHILIS  175 

bodies  for  a  long  period,  during  which  their  activity 
undergoes  fluctuations  either  spontaneously  or  as  the 
result  of  treatment.  He  considers  that  the  clinical 
course  of  syphilis  indicates  that  the  infective  agent 
(the  Spirochata  pallida)  fulfils  all  the  requirements  that 
lead  to  the  development  of  an  anaphylactic  condition 
in  syphilitic  patients.  He  therefore  concludes  that  an 
anaphylaxis  test  should  theoretically  be  as  possible  in 
syphilis  as  in  tubercle  with  Koch's  tuberculin  test,  or 
with  Von  Pirquet's  cutaneous  test,  or  in  glanders  with 
the  Malein  test.  He  uses  extracts  of  pure  cultures  of 
the  Spirochidta  pallida  as  antigen,  and  to  this  extract 
has  given  the  name  of  '  Luetin.' 

The  experiments  on  rabbits  proving  successful,  he 
proceeded  to  test  the  reaction  in  man,  using  the  intra- 
dermic  method  of  inoculation. 

Mantoux  and  Roux  in  their  original  description 
of  the  technique  of  intradermic  inoculation,  say : 
'  After  having  made  a  fold  of  skin,  the  needle  is 
pushed  in  almost  parallel  to  the  surface.  Care  must 
be  taken  that  the  bevelled  side  of  the  needle-point  is 
turned  upwards.  In  subjects  with  a  very  thin  skin  one 
must  boldly  push  the  needle  in  till  it  enters  the  hypo- 
dermic region,  and  then  elevate  the  point  and  enter  the 
dermis  from  its  under-surface.  A  fine  needle  and 
small  syringe  are  required,  which  must^  of  course,  be 
sterilized  before  use.   Only  one  drop  of  fluid  is  injected.' 

Of  250  control  non-syphilitic  cases  examined,  all 
gave  negative  reactions  ;  while  of  315  cases  of  syphilis 
at  different  stages,  213  gave  a  positive  reaction. 

Noguchi  points  out  that  theoretically  one  would  not 
expect  an  anaphylactic  reaction  to  appear  as  long  as 


176  SYPHILIS  AND  PARASYPHIUS 

the  activity  of  the  Spivochcsta  pallida  is  maintained  at 
its  maximum,  as  would  be  the  case  during  the  early 
period  of  infection.  This  theory  was  borne  out  by  the 
results  obtained,  practically  all  cases  of  primary 
syphilis  and  secondary  syphilis  with  symptoms  giving 
negative  results,  as  also  did  congenital  syphilitics  under 
one  year  of  age.  The  majority  of  cases,  however,  to 
which  the  test  was  applied  after  treatment,  with  a  con- 
sequent absence  of  symptoms  and  diminution  in  the 
activity  of  the  spirochaete,  gave  a  positive  reaction 
(see  Table  XIV.). 

Negative  Reaction. 

In  the  majority  of  normal  persons  after  twenty-four 
hours,  a  small  erythematous  area  appears  round  the 
point  of  injection  ;  there  is  no  pain  or  itching,  and  the 
reaction  passes  off  within  forty-eight  hours  and  leaves 
no  induration.  Occasionally  a  small  papule  may  be 
formed  after  twenty-four  to  forty-eight  hours,  which, 
however,  begins  to  subside  within  seventy-two  hours, 
leaving  no  induration. 

Positive  Reaction. 

This  Noguchi  divides  under  three  headings : 
I.  Papular  Form. — A  large,  raised,  reddish,  in- 
durated papule,  usually  from  5  to  10  millimetres  in 
diameter,  makes  its  appearance  in  twenty-four  to  forty- 
eight  hours.  The  papule  may  be  surrounded  by  a 
zone  of  redness.  The  dimension  and  degree  of  indura- 
tion slightly  increase  during  the  following  three  or 
four   days,  after   which   the   inflammatory   processes 


ANAPHYLAXIS  AND  SYPHILIS 


177 


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12 


178  SYPHILIS  AND  PARASYPHILIS 

begin  to  recede.     Induration  disappears  within  a  week 
in  the  majority  of  cases. 

2.  Pustular  Form. — In  this  form  at  about  the 
fourth  day  after  injection  the  papule  begins  to  soften  at 
the  centre,  and  within  twenty-four  hours  becomes  first 
vesicular,  then  pustular.  The  pustule  soon  discharges, 
and  a  scab  is  formed,  which  falls  oif  after  a  few  days. 
This  form  of  the  reaction  occurred  in  nearly  every  case 
of  tertiary  or  late  hereditary  syphilis. 

3.  Torpid  Form. — In  this,  the  least  common  form, 
the  reaction  pursues  a  course  practically  similar  to  a 
negative  reaction,  but  after  ten  days,  or  even  longer, 
the  reaction  lights  up  again  and  progresses  to  the 
formation  of  a  small  pustule. 

Noguchi  states  that  neither  in  syphilitics  nor  in  para- 
syphilitics  did  a  marked  constitutional  change  follow 
the  intradermic  inoculation  of  luetin.  In  most  positive 
cases  a  slight  rise  in  temperature  takes  place,  lasting 
for  one  day. 

The  author  up  to  the  present  has  had  no  opportunity 
of  investigating  this  test,  but  if  extended  trials  by  inde- 
pendent observers  confirm  the  results  obtained  by 
Noguchi,  it  would  appear  that  this  test  will  be  of  con- 
siderable diagnostic  value. 

As,  however,  this  test  is  not  available  for  early  con- 
genital syphilis,  primary  syphilis,  or  early  secondary 
syphilis,  it  does  not  appear  probable  that  it  will  be  of 
very  great  practical  use,  except  as  a  confirmatory  test 
in  those  cases  of  doubtful  latent  or  tertiary  syphilis 
which  fail  to  give  a  positive  Wassermann  reaction. 


CHAPTER  XVI 

LIFE  INSURANCE  AND  THE  WASSER- 
MANN  REACTION 

Syphilis  by  itself  is  accountable  for  a  comparatively 
small  number  of  deaths,  with  the  exception  of  deaths 
of  children  under  five  years  owing  to  congenital 
syphilis. 

If,  however,  the  sum  of  all  the  deaths  produced  by 
diseases  either  directly  or  indirectly  resulting  from 
previous  syphilitic  infection  be  collected  together,  a 
considerable  number  of  deaths  will  be  found  attribut- 
able to  the  SpirochcBta  pallida. 

If  to  this  already  considerable  death-rate  we  add 
deaths  from  intercurrent  diseases  having  nothing  to  do 
with  syphilis,  but  in  which  one  may  reasonably  con- 
clude that  the  resisting  power  of  the  individual  was 
lowered  by  syphilitic  infection  so  that  a  higher  death- 
rate  resulted  than  would  have  been  the  case  if  these 
diseases  had  attacked  patients  free  from  syphilis,  then 
the  death-rate  due  to  diseases  in  which  syphilis  is  one 
of  the  predisposing  causes  will  probably  be  greatly 
increased. 

REGISTRAR-GENERAL'S    REPORT 

I.  Deaths  from  Syphilis  alone.— The  Registrar- 
General's  report  for  1909  gives  the  death-rate  under 

179 


i8o  SYPHILIS  AND  PARASYPHILIS 

the  head  '  Syphilis  '  as  0-047  per  thousand  persons. 
This  includes  968  deaths  amongst  males  and  717 
amongst  females.  Far  the  greatest  number  of  deaths 
occurred  in  children  under  five  years  of  age,  and  con- 
sisted of  677  males  and  540  females.  Of  deaths 
between  the  ages  of  twenty-five  and  fifty-five,  only 
206  occurred  amongst  males  and  117  amongst  females. 
Syphilis,  therefore,  as  the  direct  cause  of  death 
amongst  adults  during  the  period  when  the  majority 
of  people  seek  insurance,  is  small. 

2.  Deaths  from  Diseases  Syphilitic  in  Origin. — 
The  deaths  from  the  three  diseases — general  paralysis, 
tabes,  aneurism  of  the  aorta — however,  which  are 
undoubtedly  syphilitic  in  origin,  give  very  different 
results. 

General  paralysis  was  given  as  the  cause  of  death 
of  1,817  males  and  546  females,  and  of  this  number 
1,386  deaths  occurred  amongst  males  and  338  amongst 
females  between  the  ages  of  twenty -five  and  fifty-five 
years.  The  total  death-rate  per  1,000  from  general 
paralysis  was  o'o66. 

The  death-rate  from  tabes  was  about  one-third  that 
from  general  paralysis,  and  about  half  the  number  of 
deaths  out  of  the  total,  both  of  males  and  females, 
occurred  between  twenty-five  and  fifty-five  years  of 
age.  ^      > 

The  death-rate  from  aneurism  is  0*033;  94^ 
occurred  amongst  males  and  221  amongst  females, 
and  of  this  number  558  and  82  respectively  occurred 
between  the  ages  of  twenty-five  and  fifty-five. 

The  total  death-rate  from  general  paralysis,  tabes, 
and  aneurism  combined,  therefore,  is  o-ii6  per  1,000, 


INSURANCE  AND  THE  WASSERMANN  REACTION    i8i 

and  the  great  majority  of  these  occurred  between  the 
ages  of  twenty-five  and  fifty-five  years. 

It  has  been  shown  in  the  previous  chapters  that 
practically  all  causes  of  general  paralysis  and  aneurism 
and  60  per  cent,  of  tabes  give  a  positive  Wassermann 
reaction,  and  in  all  probability  have  given  a  positive 
Wassermann  reaction  for  many  years  before  the  onset 
of  symptoms.  It  therefore  appears  highly  desirable, 
from  the  point  of  view  of  the  insurance  companies, 
that  the  possibihty  of  the  occurrence  of  these  diseases 
should  be  excluded  if  the  life  is  to  be  returned  as  a 
first-class  one. 

The  death-rate  per  1,000  from  all  causes  was  14*5, 
while  the  combined  death-rate  from  syphilis,  general 
paralysis,  tabes,  and  aneurism  was  0*163  per  1,000. 
One  death  in  every  eighty-eight,  therefore,  was  due  to 
syphilis,  parasyphiHs,  or  aneurism. 

Table  XV. 


Deaths  per 

Cause  of  Death. 

1,000 
Persons. 

Males. 

Females. 

All  ages 

968 

717 

Syphilis 

0-047  ] 

Under  5 

677 

540 

25  to  55 

206 

117 

f 

All  ages 

1,817 

546 

General  paralysis    . . 

o-o66  < 

Under  5 

I 

0 

[ 

25  to  55 

1,386 

33S 

I 

All  ages 

496 

123 

Tabes 

o"oi7  \ 

Under  5 

0 

0 

I 

25  to  55 

250 

59 

f 

All  ages 

946 

221 

Aneurism 

0-033  -I 

Under  5 

I 

I 

25  to  55 

558 

82 

1 82 


SYPHILIS  AND  PARASYPHILIS 


Table  XVI. 


Deaths  per 

Cause  of  Death. 

i,ooo 

Males. 

Females.  1 

Persons. 

i 

Cerebral  haemorrhage 

0-502  - 

All  ages 

7,999 

9.939 

and  cerebral  embo-     - 

Under  5 

17 

20 

lism  . . 

[ 

25  to  55 

1,289 

1,618 

Chronic    Bright's    | 
disease         . .          . .    j 

All  ages 
Under  5 

5.627 

4.877 

0294  ■ 

35 

34 

( 

25  to  55 

1,899 

1,707 

Apoplexy    and    hemi-    \ 
plegia            ..         ..  !/ 

0*226  - 

All  ages 
Under  5 
25  to  55 

3.609 

9 

540 

4,485 

7 

688 

0-149  - 

All  ages 

2,902 

2,442 

Meningitis 

Under  5 

1,862 

1. 471 

25  to  55 

325 

287 

' 

All  ages 

392 

377 

Brain  tumour 

0"022   - 

Under  5 

22 

12 

25  to  55 

192 

204 

o'o6o  - 

All  ages 

1,105 

1,023 

1  Softening  of  the  brain 

Under  5 

2 

0 

. 

25  to  55 

no 

129 

Paraplegia     and     dis-    \ 
eases  of  the  cord   . .    / 

1 

0-059  - 

All  ages 
Under  5 

1. 15'' 
47 

948 
48 

25  to  55 

400 

Per  Cent. 

311 

Per  Cent. 

All  ages 

15*4 

137 

All  causes 

14-5 

Under  5 

40-3 

33-2 

1 
i 

25  to  55 

3I-I 

24-8 

Total  deaths,  all  persons,  25  to  55,  111,122. 

,,  ,,       Table  XV..         ,,  2,996  (  =  1  in  37)  deaths. 

,,  ,,       Table  XVI..      ,,  9,699  (  =  1  in  ii)       ,, 


3.  Deaths  from  Diseases  partly  Attributable 
to  Syphilis. — The  deaths  partly  attributable  to 
syphilis  will  include  those  from  : 

1.  Cerebral  haemorrhage  and  cerebral  embolism. 

2.  i\poplexy  and  hemiplegia. 

3.  Chronic  Bright's  disease. 


INSURANCE  AND  THE  WASSERMANN  REACTION    1S3 

4.  Meningitis. 

5.  Brain  tumour. 

6.  Softening  of  the  brain. 

7.  Paraplegia  and  diseases  of  the  cord. 

Table  XVI.  shows  the  death-rate  per  1,000  persons 
from  these  diseases,  also  occurring  amongst  males 
and  females  during  the  period  of  twenty-five  to  fifty- 
five  years. 

4.  Deaths  in  which  Syphilis  may  be  a  Con- 
tributory Cause. — It  is  difficult  to  estimate  the 
deaths  occurring  in  this  class — namely,  amongst  those 
debilitated  by  syphilis,  in  which  death  might  not  have 
occurred  otherwise.  It  is,  however,  a  matter  of 
common  knowledge  that  tuberculosis  is  especially 
apt  to  develop  amongst  persons  who  have  recently 
acquired  syphilis,  and  that  tuberculosis  occurring  in 
such  subjects  is  particularly  to  be  dreaded. 


INCREASED  MORTALITY  RATE  AMONGST 
SYPHILITICS 

Brockbank  has  collected  the  following  statistics  of 
the  experience  of  assurance  companies  of  the  mortality 
of  syphilitics,  which  are  of  great  interest,  and  appear 
to  point  conclusively  to  the  importance  of  a  routine 
examination  of  the  blood  of  all  proposers  for  assurance. 
Practically  every  series  of  investigations  shows  a  con- 
siderably increased  mortality  amongst  syphilitics. 

Runeberg's  statistics  show  that  out  of  84  cases 
of  acknowledged  syphilitic  infection,  the  average  age 
of  death  was  43-4  years,  and  out  of  734  cases  that 


1 84  SYPHILIS  AND  PARASYPHILIS 

had  probably  had  syphilis,  15  per  cent,  of  the  deaths 
were  probably  directly  due  to  syphilis. 

Tiselius  recorded  650  deaths  due  to  syphilis  out  of 
5,175  persons  (i7"35  per  cent.),  and  he  recommended 
an  increased  premium  of  from  20  to  50  per  cent,  for 
each  proposal  with  a  history  of  syphilis. 

Salomonson,  out  of  121  persons  w^ho  acknowledged 
syphilis,  recorded  17  deaths  at  an  average  of  46  years, 
whereas  the  mortality  expectation  was  only  9*14. 

Blaschko  and  Jacobsohn  examined  the  causes  of 
5,724  deaths,  and  came  to  the  conclusion  that  25:5  per 
cent,  were  certainly  caused  by  syphilis,  and  40  per 
cent,  probably. 

Kleinschmidt  states  that  the  average  age  of  death 
of  eighty-eight  policy-holders  who  gave  a  history  of 
syphilis  was  47-5  years. 

Out  of  the  collected  experience  of  several  American 
insurance  companies,  the  mortality  amongst  those 
who  had  a  history  of  syphilis  was  3 3  "3  per  cent,  above 
the  expectation. 

As  it  is  acknowledged  to  be  extremely  difficult  to 
get  truthful  histories  in  regard  to  syphilitic  infec- 
tions from  candidates  wishing  to  be  insured,  and  as 
nearly  all  authorities  agree  that  syphilitics  should  be 
accepted  with  caution,  and  even  the  most  satisfac- 
tory cases  with  an  increased  premium,  the  routine 
examination  of  the  Wassermann  reaction  appears 
advisable  in  the  interest  of  the  assurance  companies. 


CHIEF    REFERENCES 


*  A  System  of  Syphilis.'     Edited  by  D'Arcy  Power 

and  J.  Keogh  Murphy. 

*  La  Syphilis.'     By  Levaditi  and  Roche. 
'Wassermann    Sero-Diagnosis   of    Syphilis    in    its 

Application  to  Psychiatry.'     By  Felix  Plant. 

*  L' Ultra  Microscope.'     By  Paul  Gastou. 
'  L'Ultra  Microscope.'     By  J.  Comandon. 

*  Serum  Diagnosis  of  Syphilis.'     By  Noguchi. 

'  Syphilis.'     By  Jas.  Macintosh  and  Paul  Fildes. 
'  Diagnosis  and  Treatment  of  Syphilis.'     By  Carl 
Browning  and  Ivy  MacKenzie. 

'  Diagnosis    of    Nervous    Diseases.'      By    Purves 
Stewart. 

'  Journal    of    the     Royal    Army    Medical    Corps.' 
Articles  by  Gibbard  and  Harrison. 

'Practitioner,'    191 1.     Review    of    'Treatment    by 
Salvarsan,'  by  Manuel  and  Bayly. 


185 


INDEX 


PAGES 

Acute  nephritis          ...             ...  ...  ...  ...  no 

After-effects  of  salvarsan             ...  ...  ...  ...  148 

Agglutination  of  Spirochceta  pallida  ...  ...  ...  7 

Alcoholism    ...              ...              ...  ...  ...  I3i>  I33 

Amyloid  disease  of  kidney          ...  ...  ...  ...  112 

Anaemia  in  syphilis      ...              ...  ...  ...  ...  37 

cause  of                 ...              ...  ...  ...  ...  38 

infantile                 ...              ...  ...  ...  ...  42 

in  parasyphilis      ...              ...  ...  ...  ...  45 

in  primary  syphilis               ...  ...  ...  ...  43 

in  secondary  syphilis           ...  ...  ...  ...  44 

in  tertiary  syphilis                ...  ...  ...  ...  45 

varieties  of            ...              ...  ...  ...  39,  40 

Anaesthesia,  Wassermann  reaction  under ...  ...  ...  90 

Anaphylaxis  in  syphilis                ...  ...  ...  ...  172 

Aneurism,  death-rate  from          ...  ...  ...  ...  181 

Anthropoid  ape  inoculations       ...  ...  ...  24,  26 

Antigen-antibody  reactions         ...  ...  ...  ...  47 

Antigen  for  Wassermann  reaction  ...  ...  ...  59 

lecithin  cholesterin               ...  ...  ...  ...  61 

normal  organ        ...              ...  ...  ...  ...  60 

requirements  of  a  good        ...  ...  ...  ...  62 

syphilitic  organ    ...              ...  ...  ...  ...  59 

titration  of             ...              ...  ...  ...  ...  61 

Aortic  aneurism,  Wassermann  reaction  in  ...  ...  90 

Apparatus  for  administration  of  salvarsan  ...  ...  136 

for  lumbar  puncture              ...  ...  ...  ...  97 

for  venipuncture  ...              ...  ...  ...  ...  63 

Arthus'  phenomenon  ...              ...  ...  ...  ...  172 

B 

Bacillus  of  Lustgarten                 ...  ...  ...  ...  i 

Bacillus  smeg7natis      ...              ...  ...  ...  ...  2 

Blindness  and  salvarsan               ...  ...  ...  ...  147 

186 


INDEX  T87 

PAGES 

Blood  and  Spirochicta  fallida     ...              ...  ...                 22,  23 

Bordet-Gengou  phenomenon      ...              ...  ...  ...       50 

C 

Cadaver,  Wassermann  reaction  in             ...  ...  ...       90 

Cancer  and  Wassermann  reaction               ...  ...  ...       89 

Cardiac  symptoms  after  salvarsan               ...  ...  ...      150 

Cerebral  sypliilis          ...              ...              ...  ...  ...      129 

tm-nour ...              ...              ...              ...  ...  133,  134 

Cerebro-spinal  fluid     ...              ...              ...  ...  96-109 

cytological  examination               ...  ...  ...       99 

in  general  paralysis      ...              ...  ...    104,  107,  127 

in  secondary  syphilis    ...              ...  ...  ...      104 

in  tertiary  syphilis        ...              ...  ...  ...      104 

lymphocytosis  of          ...              ...  ...  ...       99 

polymorphonuclear  leucocytosis  of  ...  ...      100 

quantity  of  secreted     ...              ...  ...  ...       96 

Spirochcxta pallida  in  ...              ...  ...  ...       96 

Wassermann  reaction  of              ...  ...  ...      104 

Chemical  examination  of  cerebro-spinal  fluid  ...  ...      108 

Chronic  nephritis         ...              ...              ...  ...  ...      112 

C\\\2i  oi  Spirochccia pallida         ...              ...  ...  ...          5 

C\2L's,?,\^C2it\or\  o^  Spirochceta pallida            ...  ...  ...          5 

Clinical  value  of  Wassermann  reaction     ...  ...  ...      113 

CoUes's  law  ...              ...              ...              ...  ...  ...      120 

Combined  salvarsan  and  mercury  treatment  ...  ...      157 

Complement  ...  ...  ...     46,  47,  48,  49,  50,  65 

fixation...              ...              ...              ...  ...  ...       47 

Conceptional  syphilis  ...              ...              ...  ...  ...       24 

Congenital  syphihs      ...  22,  42,  93,  95,  121,  122,  130,  143 

Contra-indications  to  salvarsan  ...              ...  ...  ...      1 50 

Control  of  treatment  by  Wassermann  reaction  ...  11 8,  119 

Corneal  inoculation     ...              ...              ...  ...  ...        25 

Culture  of  Spirochata  pallida     ...              ...  ...  ...        20 

Cytological  count,  technique  of                  ...  ...  ...      loi 

in  cerebral  syphilis       ...              ...  ...  ...      103 

in  general  paralysis      ...              ...  ...      99,  103,  127 

in  meningitis                 ...              ...  ...  ...      103 

in  secondary  syphilis   ...              ...  ...  ...      100 

in  tabes  dorsalis           ...              ...  ..."     99,  103,  129 

in  tubercular  meningitis               ...  ...  ...      104 

examination  of  cerebro-spinal  fluid    ...  ...  ...       99 

D 

Dark-ground  illumination  of  >S)^/r^r//^?/<z/^//?V/(r7      ...  ...  8 

Deaths  from  diseases  syphilitic  in  origin   ...  ...  ...      iSo 


SYPHILIS  AND  PARASYPHILIS 


Deaths  from  diseases  partly  attributable  to 

syphilis 

...      182 

from  salvarsan 

...     146 

from  syphilis  alone 

...      179 

in  which  syphilis  may  be  a  contributing  cause 

...      183 

Decomplementization  of  test-serum 

...       64 

Degeneration  of  choroid  plexus 

...      106 

Diagnosis  by  gland  puncture 

...        17 

Diarrhoea  after  salvarsan 

...      150 

Differential  diagnosis  of  spirochsetes 

...        15 

of  nervous  diseases 

...      131 

Wassemann  reaction  for 

...      115 

Disseminated  sclerosis 

133.  134 

Division  of  Spirochceta  pallida    ... 

5 

Dosage  of  mercury 

...     156 

of  salvarsan 

E 

Epilepsy 

...     140 

...     134 

Errors  in  Wassermann  reaction  ... 

83,  85 

Examination  of  chancre  for  Spirochata  pallida 

G 

General  paralysis          ...              ...              ... 

II,  12 

...     123 

cerebro-spinal  fluid  in 

127,  133 

death-rate  of 

...     181 

Wassermann  reaction  in 

104,  107,  125,  133 

Giant  forms  oi  Spirochata  pallida 

3 

Giemsa's  stain 

...       13 

Gland  puncture 

.. 

...       17 

Globulin  reaction  of  cerebro-spinal  fluid  .. 

...     108 

Gonorrhoea,  Wassermann  reaction  in 

. 

...       90 

Granule  shedding  of  Spirochceta  pallida    . . 

6 

Guinea-pig  complement 

...       65 

Gynaecology,  Wassermann  reaction  in 

TT 

. 

...     116 

H 

Habitat  of  SpirochcBta  pallida     ... 

21 

Haemoglobin 

38,41 

Haemoglobinuria 

...       43 

Hsemolytic  serum 

...       67 

from  horse    ... 

...       68 

preparation  of 

...       (>! 

titration  of    ... 

68,  69 

system  ... 

...       66 

Headache  after  salvarsan 

...     150 

Heart  disease  and  Wassermann  reaction  ... 

...       89 

INDEX 

Ilecht's  technicjue  of  Wasserniann  rcacLioi) 

Hemiplegia  ... 

Human  inoculations    ... 

Hypochondriasis 

I 

Immunity 

Importance  of  early  diagnosis  of  syphilis  ... 
Incubation  period 

Indian  ink  method  of  examination  of  SpirocJuda  pallida 
Infantile  anaemias 
Inoculation  experiments 

Insurance  candidates  and  Wassermann  reaction 
Intramuscular  injection  of  mercury  ...  156,  161, 

and  Wassermann  reaction  ...    161, 

of  salvarsan  ... 
Intraventricular  fluid   ... 

Inunction  treatment  and  Wassermann  reaction 
Invasion  of  Spirochcvta  pallida   ... 
Isolation  of  cerebro-spinal  fluid 


189 

i"A{;i':.s 
...         81 

...     28 
...    131 


J 


Jarisch-Herxheimer  reaction 


33 

18 

28 

12 

42 

24-28 

...     184 

164,  165 

164,  165 

...     168 

106 

163,  164 

21 

...     105 


150,  173 


Lardaceous  disease  of  kidney 

...      112 

Latent  syphilis  and  Wassermann  reaction 

...      113 

Lecithin  cholesterin  antigen 

61 

Leishman's  stain 

14 

Leprosy  and  Wassermann  reaction 

88 

Leucocytosis  of  blood  ... 

38 

of  cerebrospinal  fluid 

...     100 

Levaditi's  stain 

15 

Life  insurance  and  syphilis 

...     179 

and  Wassermann  reaction 

...     184 

Loefller's  stain 

14 

Luetin  reaction 

174-178 

Lumbar  puncture 

97 

Lustgarten's  bacillus    ... 

I 

Lymphocytosis  of  blood 

38 

of  cerebrospinal  fluid 

99 

M 


Malaria  and  Wassermann  reaction 

Marino's  stain 

Marriage 


13 
119 


1 90  SYPHILIS  AND  PARASYPHILIS 

PAGES 

Medicine  and  Wassermann  reaction          ...              ...  ...     115 

Mental  deficiency        ...              ...              ...             ...  130,  134 

Mercury  treatment       ...              ...              ...              ...  •••155 

and  Wassermann  reaction  ...  159,  16I;  164,  165 

Microscopical  diagnosis,  reliability  of       ...              ...  ...        19 

Moribund  persons  and  Wassermann's  reaction         ...  ...      '90 

Mortality  rate  amongst  syphilitics              ...              ...  ...      183 

Mothers  ofsyphilitic  children  and  Wassermann's  reaction  93, 121, 122 

Movements  of  S/>zroc/zce^a  pa/izda     "        ...              ...  ...  5 

N 

Narcosis  and  Wassermann  reaction 
Nature  of  Wassermann  reaction 
Negative  luetin  reaction 

Wassermann  reaction  ...  ...  91,  104, 

Neo-salvarsan 
Nephritis 

and  salvarsan 
Neurasthenia 
Noguchi's  butyric  acid  test 

luetin  test 

technique  for  Wassermann's  reaction 
Normal  organ  extract,  antigen  ... 

O 

Obstetrics  and  Wassermann  reaction 
Offspring 

Ophthalmology  and  Wassermann  reaction 
Optic  atrophy 

Original  technique  for  Wassermann  reaction 
reasons  for  superiority  of 


Paraplegia     ...  ...  ...  ...  ...  ] 

Peripheral  neuritis 

Pfeiffer's  phenomenon 

Phlebitis  and  salvarsan 

Physico-chemical  theory  for  Wassermann  reaction  ... 

Pill  treatment  and  Wassermann  reaction  ... 

Placenta  and  Spirochceta  pallida 

Pneumonia  and  Wassermann  reaction 

Polymorphonuclear  leucocytosis  of  cerebro-spinal  fluid 

Preparation  of  patient  for  salvarsan 

Primary  syphilis  and  Spirochceta  pallida  ...  ...  19 

and  ansemia  . . . 

and  luetin  reaction       ...  ...  ...  i 


90 

5 

;i-58 

117 

119, 

126 

155 

no 

»-II2 

147 

131, 

133 

108 

174 

-178 

80 

... 

68 

117, 

120 

119 

117 

134 

70 

... 

79 

133, 

134 

132 

... 

46 

147 

... 

SI 

162 

23 

89 

... 

100 

139 

',   21; 

,  22 

... 

43 

[76, 

177 

INDEX  191 

I'AGES 

Primary  syphilis  and  mercury     ...              ...  ...  ...      14" 

and  microscopical  examination  ...  ...  ...        19 

and  salvarsan                ...              ...  ...  ...      140 

and  Wassermann  reaction           ...  ...  ...       92 

Profeta's  law                 ...              ...          "   ...  ...  94,  121 

Prophylaxis  and  syphilis             ...              ...  ...  ...       3^ 

R 

Reagents  required  for  Wassermann  reaction  ...  ...        59 

Reducing  body  in  cerebro-spinal  fluid       ...  ...  ...      109 

Registrar-General's  Report         ...              ...  ...  ...      I79 

Reinfection   ...              ...              ...              ...  ...  ...        29 

Relapses  after  salvarsan  ...  ...  ...    151,  168,  170 

Relapsing  fever  and  Wassermann  reaction  ...  ...        89 

Reliability  of  microscopical  diagnosis        ...  ...  ...        19 

Resting-stage  of  Spiroc/ucta  pallida           ...  ...  ...          6 

Rigors  after  salvarsan  ...              ...              ...  ...  ...      1 50 


Salvarsan      ...              ...              ...  ...  ...  ...      135 

administration  of                  ...  ...  ...  ...      136 

after-effects  of      ...              ...  ...  ...  14S-151 

and  Wassermann  reaction  ...  ...  ...  166- 17 1 

contra-indications  to            ...  ...  ...  •••153 

dangers  of             ...              ...  ...  ...  ...      146 

deaths  follovi^ing  ...  ...  ...  ...    146,  147,  174 

in  congenital         ...              ...  ...  ...  ...      143 

in  parasyphilis      ...              ...  ...  ...  ...      144 

in  primary  syphilis               ...  ...  ...  ...      140 

in  secondary  syphilis            ...  ...  ...  ...      141 

in  tertiary  syphilis                 ...  ...  ...  ...      143 

relapses  after         ...  ...  ...  ...    151,  168,  170 

toxicity  of             ...              ...  ...  ...  ...      146 

Scarlet  fever  and  Wassermann  reaction  ...  ...  ...       89 

Schaudinn's  description  of  Spirochceta pallida  ...  ...  2 

Secondary  syphilis  and  Wassermann  reaction  ...  92,  95 

and  aneemia  ...              ...  ...  ...  ...       44 

and  cerebro-spinal  fluid  ...  ...  100,  104 

and  luetin  reaction       ...  ...  ...  176,  177 

and  salvarsan                 ...  ...  ...  ...      141 

'^^z\Aon'&i'^kmx\g'iox  Spij'ochceta pallida  ...  ...  ...        15 

Sheep's  corpuscles,  preparation  of  ...  ...  ...       66 

Simplified  techniques  for  Wassermann  reaction        ...  80-83 

inferiority  of  ...  ...  ...  81,  82,  83,  84 

Skin  diseases  and  Wassermann  reaction  ...  ...  ...       90 

Smegma  bacill us          ...              ...  ...  ...  ...         2 


192 


SYPHILIS  AND  PARASYPHILIS 


Sources  of  error  in  Wassermann  reaction 
Specificity  of  Wassermann  reaction 
of  anaphylactic  reactions     . . . 
of  antigen-antibody  reactions 
of  luetin  reaction 
Spirilla 

Spirochceta  balanitis    ... 
buccalis 
dentiuni 
pertenuis 
psetido-pallida 
refi'ingens 
Spirochceta  pallida  in  gland  puncture 
culture  of 
habitat  of 
in  blood 

in  cerebro-spinal  fluid... 
in  congenital  syphilis 
in  placenta    ... 
in  primary  syphilis 
in  secondary  syphilis  . . . 
in  semen 
invasion  of 
Spirolysis 

Staining  of  films  for  Spiroch(2ta  pallida 
Stern's  technique 
Subacute  nephritis 

Suppositories  and  Wassermann  reaction 
Surgery  and  Wassermann  reaction 
Syphilitic  organ  extract  antigen 


83-85 

86-95 

172 

48 

177 

I 

17 

15 

15 

16 

16 

17 

17 

20 

21 

22,  23 

96 

22 

23 
22 
22 
,  28 
21 
7 

13 

80 

III 

163 

116 

59 


21 


24 


Tabes  dorsalis 

cell  count  of  cerebrospinal  fluid 
death-rate  due  to 
mercury  treatment  and 
salvarsan  treatment  and 
Wassermann  reaction  in 

of  cerebro-spinal  fluid 
Technique  of  cell  count  of  cerebro-spinal 
of  luetin  reaction 
of  lumbar  puncture 
of  salvarsan  administration 
of  venipuncture     ... 
original,  of  Wassermann  reaction 
Techniques,  simplified 


m 


m 
fluid 


129 
99,  129 
...  181 
...  156 
...  144 
129,  133 
104,  129,  133 

lOI 

175 

98 

136 

63 

70 

80-83 


INDEX 

Temperature  of  antigen-antibody  action 
Tertiary  syphilis  and  ancemia 
and  luetin  reaction 
and  salvarsan  treatment 
and  Spirochicta  pallida 
and  Wassermann  reaction 

of  cerebro-spinal  fluid 
Test-serum,  preparation  of 
Testicle  inoculation 
Theobald  Smith's  phenomenon 
Therapeutic  results  of  salvarsan 
Titration  of  antigen  for  Wassermann  reaction 

of  complement  for  Wassermann  reaction 

of  haemolytic  serum  for  Wassermann  reaction 
Toxity  of  salvarsan 
Treatment  and  Wassermann  reaction 

and  Spirochceta  pallida 

by  mercury 

by  salvarsan 

combined 

importance  of  early 

of  pregnant  women 

prophylactic 
T7'eponema  pa  lliduvi   . . . 
Trypanosomiaris  and  Wassermann  reaction 
Tubercular  meningitis 
Tuberculosis  and  Wassermann  reaction 


193 

I'AGES 
...  48 

•••       45 

^n.  178 
...    143 

27, 31 

93,  95 

104 

62 

25 

172 

140 

.     61 

.  66 
68,  69 
.     146 

•  159 

35 

•  155 

•  135 

•  157 
.       18 

120 

7>S^  36 

2 

.       88 

.     104 

•  89 


U 


Urine 


no 


V 


Venipuncture,  apparatus  for 

technique  of 
Viscosity  of  Spi7-och(£ta  pallida 
Vomiting  after  salvarsan 


63 

63 

7 

150 


W 

Wassermann  reaction  ... 
and  marriage 
and  mercury  treatment 
and  salvarsan  treatment 
Flemming's  technique 
for  controlling  treatment 


159, 


...  51 
...  119 
161,  164,  165 
166-171 
...  82 
iiS,  119 


194 


SYPHILIS  AND  PARASYPHILIS 


Wassermann  reaction,  Hecht's  techniques 
in  anaesthesia 
in  aortic  aneurism 
in  cerebral  syphiHs 
in  congenital  syphilis  ... 
in  diagnosis  ... 
in  general  paralysis 
in  gynaecology 
in  medicine   ... 
in  moribund  patients   ... 
in  mothers  of  syphilitic  children 
in  narcosis     ... 
in  nonsyphilitic  diseases 
in  obstetrics  ... 
in  ophthalmology 
in  primary  syphilis 
in  secondary  syphilis   ... 
in  surgery 
in  tabes  dorsalis 
in  tertiary  syphilis 
in  the  cadaver 
nature  of 
negative 

Noguchi's  technique     ... 
of  cerebro-spinal  fluid  ... 
original  technique 
quantitative 
reagents  for 

simplified  techniques  ... 
sources  of  error  in 
specificity  of 
Stern's  technique 


PAGES 

...  8i 
...  90 
...  90 
129 
93>  95>  121,  122,  130 
...  115 
104,  107 
...     116 

115 

...       90 
121,  122 


93, 


104, 


91,  104, 


...  90 
...  88 
117,  120 
...     117 

92,  95 
29,  95 

...     116 

129,  133 

93,  95 
...       90 

51-58 

119,  126 

...       83 

104 

•••  75 
•  ••  75 
■■■  59 
...80-83 

...  S3 
...  86 
...       80 


Yaws  and  Wassermann  reaction 
Spirochcdta  pertenuis  of 


16 


Bailliere,  Tindall  ahd  Cojc,  8,  Henrietta  Street,  Covent  Garden. 


COLUMBIA  UNIVERSITY  UBRARIES 


*0H]2189626* 

HEALTH  SCIENCES  LIBRAnV 


